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At least 883 records · Page 49Linked to original sources
PubMed1991

Kinetics of N-formyl peptide receptor up-regulation during stimulation in human neutrophils.

The kinetics of receptor up-regulation was examined in isolated neutrophils and in whole blood by flow cytometry during cell activation. Stimulation of neutrophils prepared without exposure to LPS with chemoattractants induced fast up-regulation of N-formyl peptide receptors and C receptor type 3 (CR3). Biphasic N-formyl peptide binding curves were detected for saturating concentrations of N-formyl peptide at 37 degrees C. The bulk of the rapid binding during the first 30 to 60 s is attributed to already expressed binding sites whereas the slow binding over the next 3 to 4 min represents a time course of receptor up-regulation. Support for this interpretation comes from conditions under which the number of binding sites and the progress of the binding curves were affected. Cells treated with LPS, which caused expression of internal N-formyl peptide receptors, exhibited rapid, monophasic binding curves with increased total binding. In LPS-untreated, calcium-depleted cells, N-formyl peptide receptor up-regulation was inhibited and rapid, monophasic binding to a smaller total number of expressed sites was observed. Cytochalasin B enhanced the total number of available N-formyl peptide receptors in LPS-untreated but not LPS-treated cells. In both cases binding was rapid and monophasic suggesting that receptors were either fully or rapidly up-regulated. Although not studied in real-time, C receptor type 3 up-regulation was similar to N-formyl peptide receptor up-regulation in response to LPS, or stimulation by N-formyl peptide, C product C5a, leukotriene B4, and platelet-activating factor in isolated cells and in whole blood. After stimulation with formyl peptide, LPS, or C product 5a, the release of vitamin B12-binding protein paralleled up-regulation of receptors. These data indicate that untreated cells up-regulate N-formyl peptide receptors during cell response at a rate of approximately 10,000/min in a calcium-dependent manner whereas LPS-treated cells already express the bulk of their receptors. In cytochalasin B-treated, degranulating cells 30,000 to 50,000 receptors were up-regulated within a minute.

Calcium↗
PubMed1991

Stabilization of thermally labile alkylcobalamins by a haptocorrin from chicken serum.

Binding of neopentylcobalamin and benzylcobalamin to the apoprotein of a haptocorrin from chicken serum has been demonstrated spectrophotometrically. The spectra of the protein-bound cobalamins strongly resemble those of base-on alkylcobalamins and show that when unbound these sterically hindered alkylcobalamins are only approximately 75% (benzyl) and 40% (neopentyl) base-on, at neutral pH and at 5 degrees C. The haptocorrin was found to stabilize the spontaneous thermal decomposition of the neutral species of benzylcobalamin and neopentylcobalamin by 470-fold (3.6 kcal) and 166-fold (3.0 kcal), respectively, relative to the protein-free species. After correction of the activation parameters for the thermal decomposition of the protein-free, neutral alkylcobalamins for the relative proportions of base-on and base-off species, the haptocorrin was found to stabilize the base-on species of both alkylcobalamins by 275- to 1400-fold (approximately 3.3 to 4.3 kcal). From the temperature dependence of the decomposition reactions, the enthalpies of activation are found to be essentially identical for the protein-free and protein-bound species of either cobalamin. Thus, stabilization of the thermal decomposition of these sterically hindered alkylcobalamins by haptocorrin is entirely due to entropic factors.

Animals↗
PubMed1990

Additional predictive value of serum unsaturated vitamin B12 proteins in multiple myeloma.

The distribution of serum cobalamin-binding proteins was studied in 30 patients with low-grade multiple myeloma and in 26 patients with high-grade myeloma. The mean total cobalamin concentration (holotranscobalamin I and II) was similar in both groups of patients. We found a marked rise in total unsaturated binding cobalamin capacity mainly due to an increase in apotranscobalamin II (apo-TC II) in patients with high-grade myeloma. There was also a positive correlation between serum beta-2-microglobulin (B2M) and apo-TC II in myeloma patients. Our results indicate that pretreatment measurement of serum apo-TC II could supplement B2M as a prognostic guide.

Aged↗
PubMed1990

Subcellular distribution and mobilization of MAC-1 (CD11b/CD18) in neonatal neutrophils.

The CD11b/CD18 (Mac-1) heterodimeric surface glycoprotein contributes to a broad range of adherence-dependent neutrophil inflammatory functions. Previous investigations have indicated that diminished expression or regulation of Mac-1 may underlie abnormalities of stimulated adhesion and chemotaxis of neonatal neutrophils in vitro and inflammatory deficits in human neonates. To define the pathogenic mechanisms contributing to these findings, we compared the distribution and translocation of Mac-1 in subcellular fractions of neonatal and adult neutrophils before and after chemotactic stimulation. The total cell content of Mac-1 and the proportions of Mac-1 in beta fractions (vitamin B12 binding protein-rich granules), pre-gamma fractions (gelatinase-rich granules), or gamma fractions (plasma membrane) of neonatal neutrophils were comparable with those of adult neutrophils. However, after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 nmol/L, 37 degrees C, 15 minutes), neonatal neutrophils demonstrated (1) diminished translocation of Mac-1 from pre-gamma fractions (P less than .05), and (2) diminished surface expression of Mac-1 (P less than .05), as compared with healthy adult neutrophils. As shown in enzymatic and immunochemical assays, neonatal cells contained significantly (P less than .01) diminished levels of neutrophil gelatinase. In response to FMLP (0.1 to 10 nmol/L, 37 degrees C, 15 minutes), neonatal suspensions also released significantly (P less than .001) less gelatinase, as compared with adult neutrophil suspensions. These observations demonstrate that diminished mobilization of Mac-1 from gelatinase-rich granular pools in neonatal neutrophils is associated with abnormal surface expression of this glycoprotein after chemotactic stimulation. This abnormality may contribute, in part, to abnormal migratory properties of neonatal neutrophils in response to inflammatory stimuli.

Antigens, Differentiation↗
PubMed1990

A comparison of the effects of intact and deacylated lipopolysaccharide on human polymorphonuclear leukocytes.

Enzymatic deacylation of LPS markedly reduces its activity in the dermal Shwartzman reaction. Inasmuch as polymorphonuclear leukocytes (PMN) are involved in the genesis of tissue injury in Shwartzman reactions, we have investigated the effects of deacylated LPS (dLPS) on PMN. Compared to LPS, dLPS was ineffectual as a stimulus of both PMN adherence and release of secondary granule enzymes, and dLPS inhibited specific LPS-induced adherence. Neither LPS nor dLPS caused release of the primary granule enzymes, myeloperoxidase, and elastase. Unlike LPS, dLPS failed to prime PMN for superoxide release when a second stimulus (FMLP, 10(-6) M was given. The mechanism of the LPS induced increase in PMN adherence was investigated, and we found that LPS significantly increased the amount of the adhesive glycoprotein CD11b on the surface of the PMN. dLPS had no effect on CD11b expression. Our results suggest that enzymatic deacylation of LPS profoundly alters its ability to stimulate PMN and deacylation of LPS by inflammatory cells in vivo might be an important mechanism limiting the toxic effects of LPS.

Acylation↗
PubMed1990

Differential augmentation by recombinant human tumor necrosis factor-alpha of neutrophil responses to particulate zymosan and glucan.

Zymosan (Z) and its major insoluble carbohydrate component beta-linked glucan activate human neutrophils (PMN) through a trypsin-sensitive recognition mechanism. This mechanism is believed to involve the PMN CR3R. Both Z and glucan generated dose and time-dependent release of the secondary lysosomal granule marker vitamin B12 binding protein, leukotriene B4 (LTB4) and superoxide from PMN and were phagocytosed with similar dose-dependent kinetics. The PMN superoxide and LTB4 responses to glucan; however, were consistently greater than those to the same doses of Z. The phagocytosis of both particles was significantly reduced after partial digestion with beta-laminarinase but not beta-glucosidase or alpha-mannosidase suggesting a recognition mechanism dependent on intact beta-1,3-glucosidic bonds in both particles. TNF-alpha (rhTNF-alpha) promoted a time- and dose-dependent increase in the expression of PMN CR3 up to 60 min. The increased expression of CR3 was paralleled by the release of the secondary lysosomal granule marker vitamin B12-binding protein. This granule contains a population of CR3R in its boundary membrane and it is the fusion of this membrane with the plasma membrane that may represent the mechanism by which CR3 expression is increased. Preincubation of PMN with 10(-9)M rhTNF-alpha augmented phagocytosis, LTB4, and superoxide generation by PMN in response to activation by Z. In contrast, none of the responses to glucan was significantly increased after incubation with rhTNF-alpha. These differences suggest a lack of absolute homology between the recognition mechanisms for zymosan and glucan and that there is a component of the recognition mechanism for zymosan that is independent of that for glucan and is up-regulated after rhTNF-alpha pretreatment.

Glucans↗
PubMed1990

The selective augmentation by recombinant human tumour necrosis factor-alpha of neutrophil responses to pathogenic Escherichia coli.

Endotoxin release may amplify the neutrophil (PMN) responses to bacterial infection through the release of monocyte-derived tumour necrosis factor (TNF). The present study was designed to assess the effect of recombinant human TNF-alpha (rhTNF-alpha) on the in vitro response of human PMN to two defined strains of pathogenic Escherichia coli. In the absence of rhTNF-alpha, a P-fimbriate strain caused significant release of the PMN secondary granule marker vitamin B12-binding protein (B12 BP), and a low level of release of leukotriene B4 (LTB4). Type 1-fimbriate strain 504, however, stimulated the release of the primary granule marker myeloperoxidase (MPO) and PMN chemiluminescence (CL), in addition to B12 BP and LTB4 release. Following rhTNF-alpha (10(-9) M) pretreatment, the release of LTB4 by PMN stimulated with the P-fimbriate strain was synergistically augmented, while B12 BP and MPO release were additively increased. In contrast, rhTNF-alpha did not significantly affect any of the responses by the type 1-fimbriate strain. These results suggest selectivity in the priming of PMN by rhTNF-alpha and confirm the independence of PMN responses to phagocytic stimuli.

Cells, Cultured↗
PubMed1990

[Active transport of cobalamins in leukemic cells of L-1210 mice].

The Tc-II receptors of cell surface membrane and the cobalamins entering into the L-1210 mouse leukemia cells were investigated. We used the blood serum Tc-II saturated with 57CoCNCbl for radioactivity determination separately in solubilized receptors and inside of the cells. The data on ligand regulation of the leukemic cell membrane receptors number were received. The internalization of radioactive complex of Tc-II and cobalamin was revealed during intensive 3H-thymidine incorporation into DNA of the cultivated cells.

Animals↗
PubMed1989

[Experience in the determination of R-proteins in blood serum].

The blood serum R-protein was titered in 283 normal subjects to estimate the methodologic and other factors influencing the results. Among these factors is the albumin brand, which suggests that the test be made with physiologic saline. R-protein titers are different in the capillary and venous blood; in the majority of the examinees they vary in the morning and in the evening.

Capillaries↗
PubMed1989

Effects of human GM-CSF on neutrophil degranulation in vitro.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates multiple differentiated functions of mature neutrophils. Increased expression of leukocyte adhesion molecules and chemotactic receptors on GM-CSF-treated neutrophils suggested that GM-CSF may stimulate neutrophil degranulation. were assessed by quantitating the release of an exclusive component of the specific granules, vitamin B12 binding protein. Incubation of neutrophils with GM-CSF alone resulted in a significant release of [57Co]-vitamin B12 binding protein quantitatively similar to that elicited by cytochalasin B or N-formyl-methionyl-leucylphenylalanine (f-Met-Leu-Phe) alone. In addition, cells preincubated with GM-CSF and subsequently stimulated with f-Met-Leu-Phe, platelet-activating factor, or the calcium ionophore, A23187, demonstrated enhanced degranulation, which greatly exceeded that produced by GM-CSF alone. These results demonstrate a small direct effect of GM-CSF on neutrophil degranulation, as well as enhanced degranulation in cells stimulated by chemotactic agents and calcium ionophore. Neutrophil degranulation in response to GM-CSF may be involved in the phlebitis associated with therapeutic administration of GM-CSF.

Calcimycin↗
PubMed1989

[Immune deficiencies secondary to enzymopathies].

Immune deficiencies secondary to enzyme deficiencies that affect purine and pyrimidine metabolism account for approximately 50% of severe immune deficiencies inherited as a recessive autosomal trait. Adenosine deaminase (ADA) deficiency is the most common and also the earliest and most severe of these diseases. ADA deficiency is responsible for a severe combined immune deficiency with alymphocytosis and often characteristic bone and cartilage abnormalities. The treatment of choice is transplantation of compatible bone marrow; in cases where this has not been feasible, replacement therapy with the enzyme coupled to polyethylene glycol has yielded promising results. Purine nucleoside phosphorylase (PNP) deficiency is responsible for an isolated T cell defect. Low serum uric acid levels are highly suggestive of PNP deficiency. Bone marrow transplantation is indicated. In both diseases, the immune deficiency is due to the toxic effect of purine deoxynucleosides on lymphoid cells. Enzyme deficiencies that directly or indirectly affect pyrimidine metabolism (orotate phosphoribosyltransferase and methionine synthase deficiencies) are exceedingly rare and only inconsistently produce an immune defect (involving T cells).

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1989

Bidirectional effects of protein kinase C activators. Studies with human neutrophils and platelet-activating factor.

Protein kinase C (PKC) (Ca2+/phospholipid-dependent enzyme) activators stimulated human neutrophils to reduce the availability of high affinity receptors for platelet-activating factor. These effects were concentration dependent, irreversible, temperature sensitive, and antagonized by a PKC blocker. The activators also inhibited 1-O-alkyl-65% hexadecyl, 25% octadecyl-2-acetyl-sn-glycero-3-phosphocholine (PAF)-induced Ca2+ transients; this inhibition correlated precisely with receptor depletion. Contrastingly, PKC activators could enhance as well as inhibit PAF-induced degranulation. Inhibition of degranulation occurred only at concentrations of the activators which depressed high affinity PAF binding by greater than 75%. Cells treated with lesser activator concentrations responded to PAF with reduced but still substantial rises in cytosolic Ca2+, markedly increased degranulation, and markedly increased PKC mobilization. The last two responses, however, failed to occur in cells that were (a) calcium depleted, (b) treated with high activator concentrations (which inhibited virtually all PAF binding and PAF-induced Ca2+ transients), or (c) treated with PAF 5 min before a PKC activator (PAF-induced rises in cytosolic Ca2+ reversed in less than 5 min). Thus, activated PKC down-regulates high affinity PAF receptors. This tends to reduce neutrophil responses to PAF. On the other hand, PAF, perhaps by raising cytosolic Ca2+, acts synergistically with PKC activators in mobilizing PKC. This may tend to enhance function but seems capable of influencing only those responses that are elicited by PKC activators (e.g. degranulation but not Ca2+ transients). The complex and bidirectional effects of PKC activators on other receptor-mediated, calcium mobilizing agonists in various cell types may reflect these opposing mechanisms.

Calcium↗
PubMed1989

[Degradation products of cell receptors and natural antibodies in patients with various forms of pulmonary tuberculosis].

Degradation products of cell receptors, R-proteins, their products complexes with immunoglobulins, hemoreactants and natural antibodies to sheep erythrocytes, were studied in 251 patients with active tuberculosis of the lungs and in 45 healthy persons. The results were indicative of significant changes in the indices as compared to the controls and association of the changes with the clinical form phase and extent of the specific process.

Adolescent↗