SEARCH · PubMed Health

Results for “Solubility”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources

PubMed1990

Soluble and insoluble immune complexes activate human neutrophil NADPH oxidase by distinct Fc gamma receptor-specific mechanisms.

Signal transduction initiated by interaction of immune complexes (IC) with Fc gamma RII and Fc gamma RIII receptors on human neutrophils was studied by investigating the capacity of well-defined complexes to stimulate O2- generation in neutrophils. IC consisting of polyclonal rabbit antibody to human albumin were prepared at equivalence (insoluble complexes) and at five times Ag excess (soluble complexes). Stimulation of human neutrophils with soluble and insoluble IC caused a dose-dependent activation of the respiratory burst and O2- generation. Incubation of neutrophils with cytochalasin B significantly enhanced O2- generation in neutrophils stimulated with soluble IC. In contrast, cytochalasin B treatment had a minimal effect on O2- generation in neutrophils stimulated with insoluble IC. Treatment of neutrophils with PGE1 or pertussis toxin (PTx) significantly inhibited O2- generation by soluble IC-stimulated neutrophils. However, neither PGE1 nor PTx treatment significantly altered O2- generation in neutrophils stimulated with insoluble complexes. Although O2- generation induced by soluble IC was significantly inhibited by mAb against both Fc gamma RII and Fc gamma RIII receptor, insoluble IC stimulation of neutrophil O2- generation was significantly diminished only by mAb against Fc gamma RIII receptor. Cross-linking of either Fc gamma RII or Fc gamma RIII receptors on neutrophil surfaces induced O2- generation, and this activation was inhibited by both PGE1 and PTx treatment. These findings indicate that soluble and insoluble ICs induce O2- production in human neutrophils through distinct mechanisms. Soluble IC induce activation of neutrophils through a PTx- and PGE1-sensitive pathway that is dependent upon both Fc gamma RII and Fc gamma RIII receptors. Although insoluble IC induce O2- production through a PTx and PGE1 insensitive pathway mediated primarily through Fc gamma RIII receptor.

Alprostadil↗

PubMed1990

[The solubility of drugs in molten suppository bases].

Solubility of 18 drugs used in rectal therapy in molten suppository base, (Massa suppositoriorum 15, Pharmacopeia of the G.D.R. Rosupol U, 37 degrees C) is determined. Separation of drug-saturated base from drug cristals is carried out in an air-heated centrifuge followed by a partition step between petroleum ether and an aqueous medium and photometrical determination of drug concentration. The procedure leads to results with relative standard deviation of 2% (medium value of 18 drugs). The investigation gave solubility values in the range between 0.002% (theobromine) and 26% (lidocaine), whereas benzoate, phenobarbital sodium and procaine hydrochloride are completely insoluble. Sodium salicylate has an unexpected high solubility (0.48%). The solubility is temperature depended and thus the solubility enthalpy can be determined. Relations between structure and solubility are discussed for pyrazolin-5-ones and purines. A correlation between solubilities in the base and in aqueous buffer (phosphate, pH 7.4) does not exist in the series studied.

Chemistry, Pharmaceutical↗

PubMed1989

Increased non-enzymatic glycosylation and reduced solubility of skin collagen in insulin-dependent diabetic patients.

The solubility of skin collagen into acetic acid and by pepsin digestion and the degree of non-enzymatic glycosylation of collagen (ketoamine linkage) in these fractions was determined in skin specimens from 27 insulin-dependent diabetic subjects and from 17 age-matched controls. Glycosylation in acid soluble collagen specimen was significantly increased in the diabetics, 1.9 +/- 1.8 (SD)ng of hexose/micrograms of hydroxyproline in comparison to the controls. 0.9 +/- 0.8 ng of hexose/micrograms of hydroxyproline. No significant difference in this respect was noted in pepsin soluble collagen specimens. The solubility of collagen into acetic acid and by pepsin digestion were significantly reduced in the diabetics. No clear relationships between non-enzymatic glycosylation or collagen solubility and diabetic late complications (nephropathy, retinopathy or limited joint mobility) were noted. We suggest (a) that equilibrium levels of early glycosylation products are different in acid and pepsin soluble collagen specimens. (b) ketoamine linkage glycosylation products by themselves are not directly involved in diabetic late complications and (c) the solubility in acid and digestibility of collagen by pepsin may be an indicator, even though nonspecific, of increased amounts of advanced glycosylation end products.

Collagen↗

PubMed1987

Effect of amino acid at the beta 6 position on surface hydrophobicity, stability, solubility, and the kinetics of polymerization of hemoglobin. Comparisons among Hb A (Glu beta 6), Hb C (Lys beta 6), Hb Machida (Gln beta 6), and Hb S (Val beta 6).

Surface hydrophobicity, stability, solubility, and kinetics of polymerization were studied using hemoglobins with four different amino acids at the beta 6 position: Hb A (Glu beta 6), Hb C (Lys beta 6), Hb Machida (Gln beta 6), and Hb S (Val beta 6). The surface hydrophobicity increased in the order of Hb C, Hb A, Hb Machida, and Hb S, coinciding with the hydrophobicity of the amino acid at the beta 6 position. Solubility of the oxy-form of these hemoglobins decreased in relation to increases in their surface hydrophobicity, suggesting that the solubility is controlled by the strength of hydrophobicity of the amino acid at the beta 6 position. The solubility of the oxy-form of these hemoglobins is always higher than that of the deoxy-form. There is a similar linear relationship between the solubility and surface hydrophobicity among deoxyhemoglobins A, C, and Machida. However, the solubility of deoxy-Hb S deviated significantly from the expected value, indicating that the extremely low solubility of deoxy-Hb S is not directly related to the hydrophobicity of the beta 6 valine. Kinetic studies on the polymerization of deoxy-Hb Machida revealed a distinct delay time prior to polymerization. This confirms our previous hypothesis that beta 6 valine is not responsible for the delay time prior to gelation. The kinetics of the polymerization of 1:1 mixtures of sickle and non-sickle hemoglobins were similar to those of pure Hb S, suggesting that only one of the two beta 6 valines is involved in an intermolecular contact. In mixtures of equal amounts of Hb S and Hb A, Hb C, or Hb Machida, half of the asymmetrical AS, SC, and S-Machida hybrid hemoglobins behaved like Hb S during nucleation, while the other half behaved like the non-sickle hemoglobin.

Drug Stability↗

PubMed1994

Increased levels of the soluble adhesion molecule E-selectin in essential hypertension.

OBJECTIVE: To determine whether soluble E-selectin levels were raised in hypertension and whether such levels correlated with those of von Willebrand factor. DESIGN: Forty-five consecutive patients with uncontrolled hypertension (blood pressure > 140/90 mmHg) and 33 consecutive patients with controlled hypertension (blood pressure < 140/90 mmHg, i.e. normotension) were examined and compared with 40 normotensive age- and sex-matched controls. METHODS: Levels of von Willebrand factor and soluble E-selectin were measured by enzyme-linked immunosorbent assay in venous blood serum. Resting systolic (SBP) and diastolic (DBP) blood pressures were measured before venepuncture. RESULTS: Soluble E-selectin levels were raised in hypertension compared with controls and normotension. The levels of von Willebrand factor were raised in hypertension and normotension compared with controls. In multivariate analysis of all subjects, von Willebrand factor levels correlated with SBP (P < 0.001) and soluble E-selectin level correlated with DBP (P < 0.001), but levels of von Willebrand factor and soluble E-selectin did not correlate. There was no clear relationship between levels of either endothelial cell index or the class of drug therapy used or its dosage. CONCLUSIONS: We suggest that raised levels of soluble E-selectin in hypertension do not indicate endothelial cell injury but may be related to endothelial cell activation. The stimulus for release of soluble E-selectin might be different from that for von Willebrand factor.

Antihypertensive Agents↗

PubMed1993

[Serum soluble CD2, CD4 and CD8 levels in infectious mononucleosis].

Acute infectious mononucleosis (IM) is a lymphoproliferative disease caused by the Epstein-Barr virus (EBV) infection. It has been reported that soluble T cell antigens are released from cells in response to T cell activation. In the present study, we investigated whether soluble antigen levels of CD2, CD4 and CD8 in serum increase during acute IM. Soluble CD2, CD4 and CD8 levels in serum were measured by a sandwich enzyme immunoassay. In addition, peripheral blood T cell subsets were analyzed by single and two color flow-cytometric analyses in IM. Patients with IM had increased levels of soluble CD2, CD4 and CD8 in serum samples obtained during acute stages. We found a positive correlation between serum levels of soluble CD8 and absolute counts of HLA-DR+CD8+T cells during acute IM. In addition, the correlation between soluble CD8 levels and serum GOT or GPT levels was shown to be positive during acute IM. Our findings suggest that the soluble antigen levels of CD2, CD4 and CD8, in particular CD8, in serum are an important immunologic parameter for determining the activation of T cells during acute IM.

Adolescent↗

PubMed1993

Isolation and characterization of the soluble and membrane-bound porcine CD44 molecules.

Porcine CD44 was identified by the cross-reactive anti-human CD44 monoclonal antibody (mAb) Hermes-1. Material which inhibited the Hermes-1 mAb binding to porcine lymphocytes was found in porcine intestinal efferent lymph and demonstrated to be a soluble form of porcine CD44. A protocol using non-affinity techniques was established to isolate this material from porcine lymph. The isolated soluble CD44 molecule consists of a single peptide with an apparent MW of about 50,000, containing the Hermes-1 epitope. The soluble and membrane-bound forms of porcine CD44 were also affinity purified and characterized. The soluble CD44 preparation comprised a major component of 48,000-70,000 MW peptide and a minor band of 120,000 MW. The membrane-bound CD44 preparation contained a 90,000 MW major and a 120,000 MW minor component. Both the major components of the soluble and membrane-bound forms of porcine CD44 contained N-linked glycosylation. The 48,000-70,000 MW component of the soluble CD44 molecules consisted of two subsets discriminated by their binding capacity for lentil lectin and a slight difference in molecular weights. Soluble CD44 molecules were also identified in the sera of sheep, goats, horses, dogs and humans. Like the porcine counterpart, these molecules could be enriched by anion-exchange chromatography, suggesting that they have similar biochemical properties.

Amino Acids↗

PubMed1996

Soluble E-selectin in sera of patients with atopic dermatitis and psoriasis--correlation with disease activity.

E-selectin endothelial leucocyte adhesion molecule-1 is expressed on endothelial cells in distinct inflammatory skin diseases. E-selectin mediates the adhesion between activated endothelium and different inflammatory cells. To evaluate soluble E-selectin as a marker of disease activity in patients with atopic dermatitis and psoriasis, the concentration of soluble E-selectin, determined by ELISA, was studied in sera of patients before and after treatment and compared with normal non-atopic controls. The disease severity was established using clinical scoring systems. Levels of soluble E-selectin were significantly elevated in sera of patients with atopic dermatitis and psoriasis (as compared with controls). Clinical improvement, after treatment, in patients with atopic dermatitis, but not in psoriasis, was associated with a significant decrease in serum levels of soluble E-selectin. There was a significant correlation of soluble E-selectin and disease activity in patients with atopic dermatitis. These data indicate that soluble E-selectin is another parameter to evaluate the inflammatory response in atopic dermatitis and psoriasis. Determination of soluble E-selectin may be a useful measure of disease activity in atopic dermatitis.

Adolescent↗

PubMed1998

Keratin modifications and solubility properties in epithelial cells and in vitro.

The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.

Acetylation↗

PubMed1991

Elevated levels of soluble interleukin 2 receptor and tumor necrosis factor in nasopharyngeal carcinoma.

Depressed cell-mediated immunity as a measure of the mitogenic response of mononuclear cells in patients with nasopharyngeal carcinoma is well documented, but the mechanism is still unclear. The enzyme-linked immunosorbent assay was used to measure soluble interleukin 2 receptor and tumor necrosis factor levels in 295 patients with nasopharyngeal carcinoma and 97 age-matched control subjects. Soluble interleukin 2 receptor levels in patients with nasopharyngeal carcinoma were elevated and correlated with clinical staging. Higher soluble interleukin 2 receptor levels were found in patients with bone metastasis but not in patients with intracranial involvement. The levels of tumor necrosis factor in nasopharyngeal carcinoma were higher than in control subjects but did not correlate with clinical staging. These data suggest that soluble interleukin 2 receptor levels might be more useful than soluble tumor necrosis factor levels that indicate tumor bulk. Soluble interleukin 2 receptor serves as a blocking factor that competes with interleukin 2 function, resulting in a decreased mitogenic response in patients with nasopharyngeal carcinoma. The usefulness of the levels of soluble interleukin 2 receptor to monitor the efficacy of treatment in patients with nasopharyngeal carcinoma with bone metastasis requires further study.

Adolescent↗

PubMed1997

Soluble adhesion molecules (sVCAM-1 and sICAM-1) in cerebrospinal fluid and serum correlate with MRI activity in multiple sclerosis.

We performed a prospective study to correlate quantiative brain magnetic resonance imaging activity (gadolinium-diethylenetriaminepentaacetic acid enhancement) to cerebrospinal fluid and serum levels of soluble adhesion molecules in 46 patients with newly diagnosed multiple sclerosis (MS) and 30 control subjects with other diseases of the central nervous system. In all patients, magnetic resonance imaging of the brain and lumbar puncture were performed on the same day. In 32 (70%) of 46 MS patients, 8 (80%) of 10 patients with acute viral encephalitis, but none of the control subjects with noninflammatory diseases, gadolinium-enhancing lesions were detected. There was a significant correlation between the cerebrospinal fluid/serum ratios for soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 as well as serum levels for both molecules and the area of gadolinium-enhancing lesions. No obvious correlation was observed between magnetic resonance imaging findings and cerebrospinal fluid cell count, protein concentration, or intrathecal immunoglobulin production. In patients with a single periventricular gadolinium-enhancing lesion (n = 16), we observed a strong negative correlation between the distance from the lateral ventricles and the cerebrospinal fluid/serum ratios for soluble intercellular adhesion molecule-1/albumin and soluble vascular cell adhesion molecule-1/albumin. These results suggest that intrathecal production of the two soluble adhesion molecules, as well as serum levels for soluble vascular cell adhesion molecule-1, in patients with MS reflect magnetic resonance imaging activity of typical periventricular lesions.

Adult↗

PubMed1997

Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b.

Interferon beta-1b reduces clinical exacerbations and disease activity in multiple sclerosis as shown by magnetic resonance imaging, but the mechanism of action is unknown. We investigated the correlation between the levels of soluble adhesion molecules and a reduction in contrast-enhancing lesions on gadopentetate dimeglumine magnetic resonance images after treatment with interferon beta-1b. We determined levels of soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, L-selectin, and tumor necrosis factor receptor (60 kd) in monthly serum samples from patients with definite multiple sclerosis before and during treatment with interferon beta-1b. The level of soluble adhesion molecules was correlated with the number of newly enhancing lesions on monthly contrast-enhanced images. Levels of soluble vascular cell adhesion molecule during treatment were significantly increased compared to control or pretreatment values. The median levels (ng/ml) of this adhesion molecule were 580.3 (range; 373.0-640.7) for the healthy subjects, and 551.4 (489.7-875.5) for patients prior to treatment and 847.9 (591.5-1,232.9) during treatment. Levels of the other soluble adhesion molecules and soluble tumor necrosis factor receptor were not significantly changed during treatment. The increase in soluble vascular cell adhesion molecule correlated with a decrease in the number of contrast-enhancing lesions on magnetic resonance images. These data suggest a novel mechanism of action for interferon beta-1b by direct interference with the adhesion cascade, which may prevent activated T cells from trafficking into the central nervous system.

Adult↗

PubMed1989

Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease.

Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease.

Acute Disease↗

PubMed1996

Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis.

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P < 0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R) alpha and beta chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (< 1.0 pg/ml) (P < 0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r = 0.46; P < 0.0001), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69; P < 0.0001), while sIL-2R beta was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2R alpha levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.

Acute Disease↗

PubMed1997

Serum Soluble Interleukin-2 Receptor Levels in Patients with Breast Cancer.

Preoperative levels of serum soluble interleukin-2 receptor (1L-2R) were examined in 37 patients with breast cancer. We investigated the correlations of serum soluble IL-2R levels with various factors such as stage grouping, lymph node metastasis, distant metastasis, tumor size, histophthological type, estrogen receptor (ER), progesterone receptor (PgR) and CA 15-3. Serum soluble 1L-2R levels were measured with an enzyme-linked immunosorbent assay. Levels of serum soluble 1L-2R in the patients with stage III and IV breast cancer were significantly higher than those in the normal controls, and patients with stage I and II breast cancer. Preoperative levels of serum soluble IL-2R in patients with T3 and T4 were also significantly higher than those in patients with T1 and T2. Serum levels of IL-2R in patients with distant metastasis were also significantly higher than those in patients without distant metastasis. Moreover, serum levels of soluble IL-2R in patients with higher CA 15-3 were significantly higher than those in patients with normal CA 15-3 levels. We conclude that preoperative serum soluble IL-2R levels in patients with breast cancer may be a valuable parameter, especially in evaluating whether they have distant metastasis or not.

Journal Article↗

PubMed2002

The soluble Notch ligand, Jagged-1, inhibits proliferation of CD34+ macrophage progenitors.

The Notch/Notch ligand system controls diverse cellular processes. The proteolytic cleavage generates transmembrane and soluble forms of Notch ligands. We examined the effect of a soluble Notch ligand, human Jagged-1, on human cord blood (CB) CD34+ cells, under serum-deprived conditions, using soluble human Jagged-1-immunoglobulin G1 chimera protein (hJagged-1). Soluble hJagged-1 inhibited myeloid colony formation but not erythroid-mix or erythroid colony formation, in the presence of stem cell factor (SCF), interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, thrombopoietin, and erythropoietin. Cytological analysis revealed that the decrease in myeloid colonies resulted mainly from the inhibition of macrophage colony formation. Furthermore, soluble hJagged-1 led to the inhibition of macrophage colony formation supported by M-CSF plus SCF and GM-CSF plus SCF. Delayed-addition experiments and the analysis of colony sizes demonstrated that soluble hJagged-l inhibited the growth of macrophage progenitors by acting in the early stage of macrophage development. The direct action of hJagged-1 was confirmed by the enhanced expression of the HES-1 (hairy enhancer of the split-1) gene. These results suggest that soluble hJagged-1 may regulate human hematopoiesis in the monocyte/macrophage lineage.

Antigens, CD↗

PubMed2004

Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner.

AIMS/HYPOTHESIS: Vascular adhesion protein-1 (VAP-1), which is identical to semicarbazide-sensitive amine oxidase (SSAO), is a dual-function membrane protein with adhesion properties and amine oxidase activity. A soluble form of VAP-1 is found in serum, where concentrations are enhanced in diabetes and obesity. In vitro, soluble VAP-1 enhances lymphocyte adhesion to endothelial cells, thus possibly participating in the enhanced lymphocyte adhesion capacity that is implicated in the cardiovascular complications associated with diabetes or obesity. In both, the tissue origin of the soluble VAP-1/SSAO is unknown. We examined whether adipose tissue, which has abundant expression of VAP-1/SSAO, is a source of soluble VAP-1. METHODS: We detected VAP-1/SSAO in plasma of diabetic animals, with or without VAP-1 immunoprecipitation, and in culture medium from 3T3-L1 adipocytes and human adipose tissue explants. VAP-1 protein glycosylation was measured. RESULTS: Diabetic and obese animals have increased plasma SSAO activity associated with VAP-1 protein. We also found that 3T3-L1 adipocytes and human adipose tissue explants release a soluble form of VAP-1/SSAO, which derives from the membrane. The release of soluble VAP-1 was enhanced by exposure of murine and human adipocytes to TNF-alpha and blocked by batimastat, a metalloprotease inhibitor. Partial ablation of adipose tissue reduced plasma SSAO activity in normal and diabetic rats. CONCLUSIONS/INTERPRETATION: Adipose cells are a source of soluble VAP-1/SSAO released by shedding of the membrane form. The release of SSAO is regulated by TNF-alpha and insulin. By releasing VAP-1/SSAO, adipose cells could contribute to the atherogenesis and vascular dysfunction associated with diabetes and obesity.

3T3 Cells↗

PubMedDate not supplied

T-cell activation induced by anti-CD3 x anti-B-cell lymphoma monoclonal antibody is enhanced by pretreatment of lymphoma cells with soluble CD40 ligand.

T cells play a key role in the control of abnormal B cell proliferation. Factors that play a role in inadequate T cell responses include absence of expression of costimulatory and adhesion molecules by the malignant B cells and lack of cytotoxic T cells specific for tumor-associated antigens. A number of approaches have been used to enhance T cell response against malignant B cells. Agents such as soluble CD40 ligand can enhance expression of costimulatory molecules by the malignant B cells and improve their ability to activate T cells. Anti-CD3-based bispecific antibodies can retarget T cells toward the tumor cells irrespective of T cell specificity. We used the V 38C13 murine lymphoma model to assess whether the combination of soluble CD40 ligand and anti-CD3-based bispecific antibody can enhance T cell activation induced by malignant B cells more effectively than either approach alone. Expression of CD80, CD86, and ICAM-1 on lymphoma cells was up-regulated by soluble CD40 ligand. Syngeneic T cells were activated more extensively by lymphoma cells when the lymphoma cells were pre-treated with soluble CD40 ligand. Bispecific-antibody induced T cell activation was more extensive when lymphoma cells pretreated with soluble CD40 ligand were present. The combination of soluble CD40 ligand plus bispecific antibody enhanced the median survival of mice compared to mice treated with bispecific antibody alone. We conclude that pretreatment of tumor cells with agents capable of inducing costimulatory molecule expression, such as soluble CD40 ligand can enhance the ability of malignant B cells to activate T cells. This effect is enhanced by the addition of bispecific antibody. The combination of enhanced expression of costimulatory molecules and retargeting of T cells by bispecific antibody may allow for a more effective T-cell-based immunotherapy.

Animals↗