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S Horie

Publications and source records attributed to S Horie.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis.

The effects of recombinant human (rh) interleukin (IL)-4 or rhIL-13 on survival, and chemotactic activity of human eosinophils were examined. Only rhIL-13 prolonged eosinophil survival in a dose-dependent manner above 3 ng/ml. Eosinophil survival induced by rhIL-13 was inhibited by monoclonal antibodies (mAbs) against IL-3 (p < 0.01) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05), suggesting that rhIL-13 induced IL-3 and GM-CSF production from eosinophils and an autocrine mechanism is responsible for the eosinophil survival. The effects of rhIL-13 on eosinophil chemotactic activity were also examined. rhIL-13 showed chemotactic activity for eosinophils in a dose-dependent manner. Checkerboard analysis revealed that eosinophil migration was dependent on the concentration gradient, confirming that rhIL-13 is a chemotactic factor. rhIL-4 showed no effects. IL-13 may play an important role in the survival and recruitment of eosinophils in allergic diseases.

Cell Degranulation↗
PubMed1997

Inhibitory effects of theophylline and procaterol on eosinophil function.

Eosinophils play a crucial role in bronchial asthma. As theophylline and procaterol (beta 2-agonist) are used for the treatment of bronchial asthma, the specific functions of eosinophils in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet activating factor (PAF) were examined using theophylline and procaterol alone and in combination. Eosinophil degranulation induced by PAF or GM-CSF was inhibited by theophylline (10(-6) M-10(-3) M and 10(-6) M to 10(-3) M, respectively) and procaterol (10(-7) M-10(-5) M and 10(-7) M-10(-5) M, respectively). The combination of 10(-4) M theophylline and various concentrations of procaterol provided higher inhibition than 10(-4) M theophylline or procaterol (10(-7) M-10(-5) M). CD11b, which is a triggering molecule for human eosinophil degranulation, showed a significantly inhibited expression of PAF stimulation with 10(-4) M theophylline. CD11b and another triggering molecule for eosinophil degranulation, CD18, showed a significantly inhibited expression of PAF stimulation using a combination of 10(-4) M theophylline and various concentrations of procaterol (10(-5) M-10(-7) M) compared with the inhibition of 10(-4) M theophylline or procaterol (10(-5) M-10(-7) M), but GM-CSF-stimulated eosinophils were not inhibited. Taken collectively, theophylline and/or procaterol have anti-inflammatory effects.

Asthma↗
PubMed1997

Detection of large macrophage colony forming cells in the peripheral blood of patients with rheumatoid arthritis.

OBJECTIVE: To test for the presence of colony forming cells, that form large macrophage colonies (> 2.5 mm in diameter, > 10,000 cells), in the peripheral blood of patients with rheumatoid arthritis (RA) and to determine its association with the clinical and laboratory features of RA. METHODS: Peripheral blood mononuclear cells (PBMC) from 96 patients with RA and 20 healthy controls were assayed for in vitro colony formation. In addition, PBMC from 38 patients with other rheumatic diseases including systemic lupus erythematosus (SLE), progressive systemic sclerosis (SSc), and polymyositis/dermatomyositis (PM/DM); 23 patients with infectious inflammatory diseases were also assayed. RESULTS: Large macrophage colony forming cells were detected in the peripheral blood of 19% of patients with RA (18/96), but not in that of healthy controls. In addition, these cells were detected in the peripheral blood of 11 of the 38 patients with other rheumatic disease (7/13 SSc and 4/11 PM/DM), but not in the 23 patients with infectious diseases. In the patients with RA, interstitial lung disease was significantly more frequently observed among patients in whom colony forming cells were found than among those in whom they were not found (p < 0.001). CONCLUSION: Based on the size of the colonies they formed, the macrophage colony forming cells detected in patients with RA probably corresponded to primitive hematopoietic progenitor cells, defined as high proliferative potential colony forming cells (HPP-CFC). Our observations provide preliminary evidence of the appearance of HPP-CFC in the circulation during inflammation of RA, and during that in other rheumatic diseases such as SSc and PM/DM, and of the association of HPP-CFC with interstitial lung disease in patients with RA.

Adult↗
PubMed1997

Effect of oxidized low density lipoprotein on thrombomodulin expression by THP-1 cells.

We have investigated the effects of oxidized low density lipoproteins (oxidized LDL) on the expression of TM by THP-1 monocytic cells. TM antigen levels and its cofactor activity for thrombin-dependent protein C activation were increased by oxidized LDL and accompanied by an increase in TM mRNA levels. Incubation of THP-1 cells with 300 microg/ml oxidized LDL for 24 h resulted in an 80% increase of cellular TM antigen levels. Native LDL and acetylated LDL did not affect the TM expression by these cells. The resultant aqueous phase after extraction of oxidized LDL by chloroform/methanol increased the TM antigen levels as well as oxidized LDL. Phorbol 12-myristate 13-acetate (PMA) also increased the TM antigen level 2.1 times the control and was accompanied by the adhesion of cells to plastic dishes and increasing macrophage cell surface antigen CD14 levels. In contrast, oxidized LDL did not induce differentiation to the macrophage. The present results indicate that oxidized LDL increases cellular TM antigen without cellular differentiation and that up-regulation of TM by oxidized LDL in monocytes may have some implication in atherosclerosis.

Arteriosclerosis↗
PubMed1997

Inhibition of accelerated coronary atherosclerosis with short-term blockade of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in a heterotopic murine model of heart transplantation.

BACKGROUND: Graft arteriopathy limits the long-term survival of allograft recipients. Cardiac allografts in mice develop graft coronary arteriopathy similar to that observed in clinical chronic rejection in human beings. We found that antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs) induce immunologic tolerance to mice with cardiac allografts. METHODS: To evaluate the effects of short-term administration of anti-ICAM-1 plus anti-LFA-1 mAbs in preventing graft arteriopathy, we treated C3H/He mice that received cardiac allografts from BALB/c mice with anti-ICAM-1 plus anti-LFA-1 mAbs for the first 5 days after transplantation. For control studies, FK506 was administered daily to other allograft recipients. Allografts were harvested on day 60. Immunohistochemical analysis was used to detect the expression of ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and in situ reverse transcriptase polymerase chain reaction was performed to detect platelet-derived growth factor (PDGF)-B mRNA expression in the graft arteries. RESULTS: Allografts from mice that received FK506 treatment daily showed significant neointimal thickening with increased expression of ICAM-1, VCAM-1, and PDGF-B mRNA, whereas there was almost no intimal thickening and ICAM-1, VCAM-1, and PDGF-B mRNA expression in the mice that received anti-ICAM-1 plus anti-LFA-1 mAbs. CONCLUSION: Short-term blockade of ICAM-1 and LFA-1 adhesion not only induces immunologic tolerance to cardiac allografts but also prevents graft arteriopathy.

Animals↗
PubMed1997

Assessment of tolerance induction to cardiac allograft by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.

BACKGROUND: Transplantation tolerance is induced by selective manipulation of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) molecules in the adult mouse. However, the mechanism of this tolerance induction has not been elucidated. METHODS AND RESULTS: C3H/He mice were heterotopically transplanted with BALB/c hearts; recipients were injected with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAbs). Of 3-day administration of both mAbs at 50 micrograms/day, all recipients accepted cardiac allografts indefinitely (n = 20); this also occurred in 5 of 10 mice that were not treated until day +4 or day +5. Long-term cardiac allograft acceptance was also achieved in thymectomized recipients. This tolerance could not be abrogated by the injection of either naive recipient lymphocytes or sensitized lymphocytes taken from the recipient strain mice that rejected the same donor strain hearts. Mixed lymphocyte culture showed that splenocytes from allograft recipient mice treated with the mAbs showed normal allogeneic response without donor alloantigen specificity. CONCLUSIONS: These results demonstrate the unique character of the peripheral tolerance induced by anti-ICAM-1 and anti-LFA-1 mAbs. Further studies are required to elucidate detailed mechanisms of transplantation tolerance development.

Animals↗
PubMed1996

Oxidized low density lipoprotein reduces thrombomodulin transcription in cultured human endothelial cells through degradation of the lipoprotein in lysosomes.

Oxidized low density lipoprotein (LDL), a potent atherogenic lipoprotein, has been shown to cause the alteration of various endothelial functions. We have examined the effect of oxidized LDL on the cofactor activity for thrombin-dependent protein C activation and expression of thrombomodulin (TM), a cell surface antithrombotic glycoprotein, on cultured human umbilical vein endothelial cells. Oxidized LDL prepared by irradiation of LDL with 254-nm ultraviolet light did not directly affect the cofactor activity of isolated TM. Exposure of the cells to oxidized LDL (25-200 microg/ml), but not native LDL and acetylated LDL, reduced TM cofactor activity in parallel with its antigen levels on the cell surface in an oxidation-, concentration- and time-dependent manner. TM mRNA levels were reduced prior to decrease in TM antigen levels and were 50% of the control levels at 3.0 h after treatment of the cells with oxidized LDL. The apparent half-life time (t1/2 = 2.8 h) of TM mRNA in the oxidized LDL-treated cells, however, did not significantly differ from that (t1/2 = 2.6 h) in the control cells when the cells were coincubated with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a transcriptional inhibitor. Treatment of the cells with bafilomycin A1, an inhibitor for the proton pump of the lysosomes, inhibited intracellular degradation of the LDL and prevented down-regulations of the mRNA and the cell surface TM antigen levels caused by oxidized LDL. The inhibitor molecule in oxidized LDL was shown to be a lipid; organic solvent extracts (300 mg/ml cholesterol, an equivalent concentration with lipids in 200 microg/ml oxidized LDL) of oxidized LDL inhibited expression of TM antigen to nearly the same extent as the oxidized LDL, although water extracts did not affect TM expression on the cells. These results suggested that down-regulation of TM on endothelial cells exposed to oxidized LDL resulted from inhibition of its transcription mediated by lysosomal degradation of oxidized LDL and that a lipid component in the LDL could be an active species. A decrease in TM expression on the surface of endothelial cells may contribute to promote thrombosis in atherosclerotic lesions.

Anti-Bacterial Agents↗
PubMed1996

Extracellular matrix proteins attenuate activation and degranulation of stimulated eosinophils.

Cellular adhesion plays an important role in the recruitment and activation of eosinophils. Here, we investigated whether extracellular matrix (ECM) proteins modify effector functions of activated human eosinophils. We coated 96-well plates with laminin or fibronectin and blocked nonspecific protein-binding sites with human serum albumin (HSA). When eosinophils were stimulated with platelet-activating factor (PAF) and incubated in these ECM-coated wells, the eosinophils adhered using both beta 1- and beta 2-integrins. Degranulation of eosinophils adherent to laminin- and fibronectin-coated wells was reduced about 50% compared with cells adherent to uncoated, HSA-blocked wells. Furthermore, these inhibitory effects of laminin and fibronectin were concentration-dependent and secretagogue-specific, that is, degranulation induced by C5a and IL-5 was inhibited while degranulation induced by secretory IgA and PMA was not inhibited. Plasma fibronectin, type I collagen and type IV collagen also inhibited PAF- and C5a-induced eosinophil degranulation, whereas fibrinogen did not. By microscopy, PAF-stimulated eosinophils, adhering to uncoated HSA-blocked wells, appeared elongated with many pseudopods. In contrast, eosinophils adhering to laminin-coated wells appeared oval with few pseudopods. Furthermore, when cells were incubated in laminin-coated wells, PAF-stimulated production of a second messenger, inositol phosphate, was markedly reduced. These findings suggest that ECM protein, such as laminin and fibronectin, attenuate both activation and degranulation of eosinophils and also influence their morphology after stimulation by physiologic secretagogues. Thus, ECM proteins may regulate activation of eosinophils, as they traverse between the peripheral blood and their targets.

Cell Adhesion↗
PubMed1996

Detection of alpha 1-adrenoceptor subtypes in human hypertrophied prostate by in situ hybridization.

Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via the alpha 1 adrenoceptor, and the results of pharmacological studies suggested the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha 1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated their expression in the tissues of ten cases of benign prostatic hypertrophy, using in situ hybridization. To determine the ratio between these subtypes, an RNase protection assay was also performed in three cases. Expression of the alpha 1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the interstitium, but was absent in glandular epithelial cells. On the contrary, the alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1. These results supported the idea that the differences in prostatic contractile response to several adrenergic drugs are based on the affinities of these drugs for the different subtypes.

Aged↗
PubMed1996

Neurogenic stimulation of gastric acid secretion by the Na+, K(+)-ATPase inhibitor ouabain in mouse isolated stomach.

1. We have previously found the stimulatory effect of ouabain on gastric acid secretion. In the present study, we further studied the ouabain-induced acid secretion in mouse isolated stomach. 2. In the resting stomach preparation, ouabain produced a transient increase in basal acid secretion, which was followed by a fall to the level lower than the initial basal level. 3. The ouabain-induced acid secretion was abolished by tetrodotoxin or atropine, and was partially inhibited by hexamethonium or famotidine. High K+ solution potentiated the ouabain stimulation. 4. Endogenous ouabain has been recently identified in plasma of humans, but the physiological roles of this compound have not yet been defined. The present study in mouse isolated stomach showed that ouabain induced a transient increase in gastric acid secretion through the release of endogeneous acetyl-choline, and subsequently inhibited acid secretion. It therefore seems likely that endogeneous ouabain modifies gastric acid secretion in physiological and pathological conditions.

Animals↗
PubMed1996

Cytokines directly induce degranulation and superoxide production from human eosinophils.

BACKGROUND: Cytokines are implicated in allergic diseases and can modulate effector functions of eosinophils stimulated by another agonist. However, little is known about the capacity of cytokines to directly trigger eosinophil degranulation. OBJECTIVES: We attempted to determine whether cytokines can directly induce degranulation and superoxide production from eosinophils. METHODS: Eosinophils from normal donors were incubated with various cytokines in albumin-coated tissue culture plates for 4 hours. To quantitate degranulation, the amounts of eosinophil-derived neurotoxin in supernatants were measured by radioimmunoassay. In addition, superoxide production was measured by superoxide dismutase-inhibitable reduction of cytochrome c. RESULTS: IL-5, IL-3, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor- alpha, and RANTES all induced eosinophil degranulation. Granulocyte-macrophage colony-stimulating factor was the most potent and induced eosinophil-derived neurotoxin release comparable to that induced by secretory IgA beads, one of the most potent secretagogues for eosinophils. In addition, IL-5 and tumor necrosis factor- alpha were synergistic in their induction of eosinophil degranulation. In contrast, IL-1, IL-8, interferon- gamma, and macrophage inflammatory protein-1 alpha did not induce degranulation. Finally, IL-5, IL-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor- alpha, but not RANTES, also induced superoxide production from eosinophils. CONCLUSIONS: Certain cytokines directly induce eosinophil degranulation and superoxide production in vitro. Therefore these cytokines may be important in the release of toxic granule proteins from eosinophils in allergic diseases.

Cell Degranulation↗
PubMed1996

Analysis of recombinant human tumour necrosis factor-alpha-induced CD4 expression on human eosinophils.

We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-alpha (rhTNF-alpha) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-alpha induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-alpha-induced CD4 expression was significantly inhibited by 10(-6) M cycloheximide, 10(-8) M dexamethasone, or 10(-6) M herbimycin A. Recombinant human interferon-gamma inhibited rhTNF-alpha-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-alpha-induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity.

Benzoquinones↗
PubMed1996

Immunological analysis of organized pneumonia with eosinophilic pleural effusion.

A 73-year-old man developed organized pneumonia with severe right-sided eosinophilic pleural effusion (PE). CD69+ and HLA-DR+ eosinophils in PE were 90 and 31%, respectively, but were undetectable in peripheral blood (PB). CD4+, CD45RA+ (naive) and CD4+, CD45RO+ (memory) cells in PB, PE and bronchoalveolar lavage (BAL) were 10.9, 8.4, 2.5 and 22.7, 38.3 and 16.4%, respectively. CD8+, CD45RA+ (naive) and CD8+, CD45RO+ (memory) cells in PB, PE and BAL were 3.5, 4.7, 1.0, and 8.9, 11.3 and 46.0%, respectively. The concentrations of interleukin-5 (IL-5) and IL-6 in PE were 1,680 and 2,797 pg/ml, respectively; however, these cytokines were undetectable in PB. The patient died 1 month after surgery to remove right thickened pleura. Microscopic findings showed right fibrinous pleuritis and organized pneumonia.

Aged↗
PubMed1996

Effects of weight cycling on coronary risk factors.

Interest in the health hazards of weight loss and regain (weight cycling) is growing. This study examined the relationship between weight cycling during ages 21 to 35 and changes in coronary risk factors (systolic blood pressure, diastolic blood pressure, total cholesterol, and HDL cholesterol) during ages 35 to 40. We followed up 264 blue-collar workers from the time they were 21 to 40 years of age working for one company. Analysis of covariance was applied including the number of weight cycles during ages 21 to 35 as the independent variable and the changes in coronary risk factors between age 35 and 40 as the dependent variables. The covariates were adjusted for body mass index (BMI) at age 35, increase in BMI between ages 35 and 40, value of coronary disease risk factors at age 35, and smoking status at age 40. The results showed that increase in systolic and diastolic blood pressure was not significantly related to the number of weight cycles. For total and HDL cholesterol, interaction was seen between smoking status and the number of weight cycles, and the effects of weight cycle on cholesterol levels were examined by smoking status. The change in total cholesterol among frequent cyclers was not significantly different from that among non-cyclers. Though the increment of HDL cholesterol in frequent cyclers was significantly larger than that in non-cyclers for non-smokers, an inverse relationship was seen for heavy smokers (not significant). Our results showed the effects of weight cycling on changes in coronary risk factors only for HDL cholesterol based on analysis by smoking status. As the present study was conducted on a small population, interaction between weight cycling and smoking status on HDL cholesterol should be confirmed using a larger population.

Adult↗
PubMed1996

An evaluation of various indices of body weight change and their relationship with coronary risk factors.

OBJECTIVE: To compare interrelationships between different indices and their relationship with cardiovascular disease risk factors. METHOD: Longitudinal comparison among weight change indices in the observation of a fixed population from age 21-40. SUBJECTS: 215 non-obese blue-collar workers in a steel company. MEASUREMENTS: Systolic blood pressure, diastolic blood pressure, serum cholesterol, serum uric acid, past history of illness, present illness, body mass index (BMI: weight/height2 (kg/m2)), indices of weight change (the intrapersonal standard deviation of BMI (ISD), the coefficient of variation of BMI (CV), the root mean square error of variation (RMSE) around the slope of BMI vs age, weight change categories (cycler, weight gainer, no changer, etc.), and number of weight cycles (NWC: one cycle is defined as 5% weight loss and 5% weight gain)). Indices were calculated using yearly and five-yearly measurements of weight for analyses. RESULTS: The average RMSE distinguished large cyclers from other weight change categories, while ISD and CV did not. The correlation between ISD and CV was strong and significant. That between RMSE and ISD (or CV) was moderate and significant. Among the weight change categories, no weight change group included many actual weight cyclers. As for the relationship with coronary risk factors, no significant change in risk was noted in cyclers as determined by NWC or weight change category. The top one third of ISD and the top one third of CV was related with elevated risk of "any risk factor,' but at a lower level of significance. CONCLUSION: ISD and CV reflect almost the same aspects of weight change, but the other indices reflect different aspects. When investigating the relationship between coronary risk factors and weight variability (especially, weight cycling) among young adult non-obese men, it is preferable to use weight change patterns such as NWC and weight change categories, or RMSE in conjunction with or in place of CV (or ISD).

Adult↗
PubMed1995

A crucial role for beta 2 integrin in the activation of eosinophils stimulated by IgG.

An IgG-coated surface, such as found on parasites, is one of the most effective physiologic stimuli for eosinophil activation. Recent evidence suggests that cellular adhesion, especially that through the beta 2 integrin, is an important step in cellular activation and accumulation. Therefore, we investigated the role of adhesion molecules in IgG-stimulated eosinophil functions. Cross-linking of eosinophil cytophilic IgG by anti-IgG immobilized to tissue culture plates induced degranulation, whereas soluble anti-IgG did not. Similarly, eosinophils exposed to human IgG immobilized to plates adhered and degranulated; in addition, adherence and subsequent degranulation were inhibited by mAbs to CD18 and CD11b, but not by mAb to CD29, suggesting an important role of beta 2 integrin for these responses. Eosinophil degranulation induced by IgG covalently coupled to Sepharose 4B beads was also inhibited by mAb to CD18. Furthermore, fibrinogen, a ligand for CD11b/18, showed synergistic enhancement of IgG-induced degranulation when it was co-immobilized with IgG to plates. A morphologic study showed that eosinophils, stimulated by immobilized IgG, protrude numerous pseudopods; this morphologic change was inhibited by mAb to CD18. This cellular adhesion seems to affect the early signaling events in eosinophils because the production of inositol phosphates was abolished by mAb to CD18. Interestingly, although superoxide production by eosinophils triggered by immobilized IgG was inhibited by mAb to CD18, superoxide production and morphologic change of neutrophils were not. These results suggest that cell adhesion through CD11b/18 is a crucial step for the activation, signaling, and effector function of eosinophils stimulated by IgG.

Antibodies, Monoclonal↗