摘要:

AbstractIntcrleukin‐9 (IL‐9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2‐like T cell responses in vivo. The IL‐9 receptor is a member of the hemopoietin receptor superfamily and interacts with the γ chain of the IL‐2 receptor for signal transduction. Various observations indicate that IL‐9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL‐9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL‐9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL‐9 results in the development of thymic lymphomas. In the human, the existence of an IL‐9‐mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL‐9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines.J. Leukoc. Biol. 57: 353–360; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.353

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMacrophages (Mφs) undergo a physiological response known as the macrophage disappearance reaction (MDR) in response to certain stimuli in the peritoneal compartment. The types of stimuli that can cause the MDR, the relationship of the MDR to the host immunological response, and the possible role of the MDR in Mφactivation are reviewed. The data indicate that the MDR occurs in response to both acute nonspecific inflammatory and specific immune delayed hypersensitivity processes and that the MDR may play an important role in Mφactivation.J. Leukoc. Biol. 57: 361–367; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.361

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe potential role of intercellular adhesion molecule‐1 (ICAM‐1) in the pathogenesis of reperfusion injury was investigated in male Fischer rats subjected to 45 min of hepatic ischemia and 24 h of reperfusion. ICAM‐1 mRNA levels increased during ischemia in the ischemic liver lobes; however, during reperfusion mRNA levels increased in both the ischemic and nonischemic lobes. Immunohistochemical evaluation indicated ICAM‐1 expression only on sinusoidal lining cells in controls; ischemia‐reperfusion enhanced ICAM‐1 expression in the sinusoids and induced some expression on hepatocytes. The monoclonal anti–ICAM‐1 antibody 1A29, but not an immunoglobulin G control antibody, administered at 1 h and 8 h of reperfusion (2 mg/kg) significantly attenuated liver injury as indicated by 51% lower plasma alanine aminotransferase activities and 32–36% less hepatic necrosis at 24 h without affecting reactive oxygen formation by Kupffer cells and hepatic neutrophils. Although 1A29 reduced neutrophil extravasation in a glycogen peritonitis by 60%, the antibody had no significant effect on hepatic neutrophil infiltration during reperfusion. These data suggest that ICAM‐1 plays a significant role during the neutrophil‐dependent injury phase after hepatic ischemia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure.J. Leukoc. Biol. 57: 368–374; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.368

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have measured the immunoreactive neutrophil elastase (ir‐NE) concentration in tumor extracts of 313 primary human breast cancers using an enzyme‐linked immunosorbent assay recently developed and have evaluated its association with disease‐free survival. This is a sensitive assay that enables rapid measurement of both free‐form and α1‐proteinase inhibitor (α1‐PI)–complexed form of ir‐NE. Breast cancer patients with high ir‐NE concentrations had a significantly shorter disease‐free survival (P= .013) than those with a low ir‐NE concentration at the cutoff point of 9.0μg/100 mg protein, which was determined in another group of 49 patients. In multivariate analysis, the ir‐NE level was found to be an independent prognostic factor (relative risk = 2.2,P= .025) for disease recurrence in human breast cancer. Furthermore, when multivariate analysis was repeated with inclusion of each level of free‐form and α1‐PI‐complexed form, the former level was an independent predictor of recurrence (relative risk = 2.5,P= .015), whereas the latter was not independently predictive (P= .43). These results support the hypothesis that this enzyme may play an active role in the tumor progression that leads to metastasis in human breast cancer.J. Leukoc. Biol. 57: 375–378; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.375

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractLeukocytes come into intimate contact with the venular endothelium as they extravasate from blood to the interstitium during inflammation. In exteriorized tissues, the number of leukocytes rolling along the vessel wall was markedly increased in adrenalectomized and metyrapone‐treated animals, relative to sham‐operated and normal animals. During the development of an acute, local inflammatory response, rollers were numerically decreased and a stronger adhesion of the cells to the endothelium, with a concomitant migration into tissues, was observed. Adhesion and migration were much more marked in adrenalectomized and metyrapone‐treated animals than in controls, suggesting that secreted glucocorticoids exert a suppressive effect on leukocyte‐endothelial interactions. The increased number of rolling leukocytes in adrenalectomized and metyrapone‐treated animals apparently resulted in more cells available to migrate into inflamed tissues. The effect appears to involve receptor occupancy and induction of gene expression because normal animals receiving the steroid antagonist RU 38 486, actinomycin D, or cydoheximide behaved as adrenalectomized or metyrapone‐treated animals. Administration to adrenalectomized animals of a monoclonal antibody to the membrane glycoprotein complex GD18 did not affect the number of rolling cells, but dramatically reduced the number of adherent or migrated leukocytes. It is suggested that secreted glucocorticoids, in addition to an effect on rolling behavior of circulating leukocytes, might also modulate the activity of the glycoprotein complex CD18 on white blood cells. The ultimate consequence is a restrictive effect on cell emigration in inflammation.J. Leukoc. Biol. 57: 379–386; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.379

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMurine monoclonal antibodies (mAbs) to humanβ2‐glycoprotein I (β2GPI), a plasma protein required for the binding of some antiphospholipid antibodies, have been shown to possess lupus anticoagulant properties and to activate platelets via Fcγ receptor (FcγR) crosslinking. Here we investigated their ability to induce polymorphonuclear leukocyte (PMN) functional responses. The six mAbs (IgGl isotype) tested in combination withβ2GPI led to a concentration‐dependent activation of human PMNs as appreciated by granule release, H2O2production, and cytosolic Ca2+increase. This activation process was accompanied by the enhancement of PMN‐mediated heparan sulfate loss from the endothelial cell line EA.hy 926 without evidence for cell lysis or detachment. F(ab')2fragments of one of the mAbs bound to PMNs in aβ2GPI‐dependent manner but were devoid of activating effects. Carbamylatedβ2GPI was unable to mediate PMN‐antibody binding and subsequent activation. In addition, cationization ofβ2GPI or removal of its sialic acid groups led to higher efficiency in binding to the PMN surface and triggering activation in comparison with the untreated protein. Thus, the process of PMN activation depends on mAb binding to these cells through both Fab (viaβ2GPI) and Fc domains, as confirmed by the suppression of all responses upon treatment with an anti‐FcγRII, but not anti‐FcγRIII, antibody. Our data suggest a model of cellular activation byβ2GPI‐dependent antiphospholipid antibodies.J. Leukoc. Biol. 57: 387–394; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.387

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have previously reported that human airway macrophages do not respond to theβ‐adrenoceptor agonist isoprenaline. The airway macrophage is known to be derived from the blood monocyte. In this study we have assessed the effect ofβ‐adrenoceptor stimulation on human monocytes matured into macrophages in vitro, to determine whether the lack of response previously observed in the airway macrophage may be a consequence of differentiation. The release of thromboxane B2(TXB2) from freshly isolated monocytes stimulated by opsonized zymosan (OPZ) was inhibited by 39.3 ± 5.5% in the presence of isoprenaline (10‐7M). However, the response was lost in the monocyte‐derived macrophage (MDM), where isoprenaline (10‐7M) caused only 4.0 ± 9.3% inhibition of OPZ‐stimulated TXB2release. In contrast forskolin (10‐5M) inhibited MDM TXB2release by 36.4 ± 17.3%, indicating that the adenylyl cyclase was functional. Measurement of adenylyl cyclase activity showed that there was a reduction in the basal level, 17.03 ± 4.1 to 7.9 ± 4.6 cyclic AMP pmol/min/mg protein, and NaF (10‐2M)‐induced activity, 116.3 ± 32.1 to 21.9 ± 12.6 cyclic AMP pmol/min/mg protein, between freshly isolated monocytes and MDMs, respectively. In addition, there was no change in MDM basal adenylyl cyclase activity on exposure to isoprenaline. Thus we have demonstrated the loss ofβ‐adrenoceptor function during the maturation of human monocytes to macrophages in vitro, despite a functional adenylyl cyclase system. In this respect the monocyte‐derived macrophage is like the airway macrophage.J. Leukoc. Biol. 57: 395–400; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.395

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractRetinoic acid (RA) and 1,25‐(OH)2‐vitamin D3(1,25‐D3) induced U937 cell maturation into distinct monocytic phenotypes, as demonstrated by up‐regulation of CD23 by RA and CD14 by 1,25‐D3. Differentiation by RA but not by 1,25‐D3was associated with reduction of basal and complete suppression of interferon‐γ (IFN‐γ)–stimulated intercellular adhesion molecule 1 (ICAM‐1) expression. Induction of cyclooxygenase activity by RA and attenuation of basal ICAM‐1 expression exhibited similar kinetics. Treatment with indomethacin prevented and prostaglandin E2(PGE2), dibutyryl‐cAMP, or forskolin mimicked reduction of basal ICAM‐1 expression by RA, indicating that this effect of RA is mediated by PGE2synthesis and subsequent cAMP elevation. In contrast, suppression of IFN‐γ‐induced ICAM‐1 expression by RA was only partly reversible by indomethacin, suggesting that inhibition of IFN‐γ stimulation was not completely due to cyclooxygenase induction. RA did not always counteract IFN‐γ, as it cooperated with IFN‐γ in down‐regulating very late activation antigen 4. Specific polymerase chain reaction and Northern blotting of ICAM‐1 mRNA revealed that RA suppressed ICAM‐1 induction by IFN‐γ at the transcriptional level. RA also blocked ICAM‐1 induction by IFN‐γ in isolated human blood monocytes. In conclusion, inhibition of basal and stimulated ICAM‐1 expression in monocytic cells may provide a mechanism for beneficial anti‐inflammatory effects of retinoids. J. Leukoc. Biol. 57: 401–406; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.401

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe investigated the role of mucin‐type (O‐linked) carbohydrate chains of tumor target cells in the recognition by macrophages through a Gal/GalNAc‐specific calcium‐dependent lectin. Binding of a soluble form of this lectin to P815 mastocytoma cells was increased by treatment with benzyl‐GalNAc, which presumably inhibited the extension of mucin‐type carbohydrate chains. The levels of cell surface expression of GalNAc residues were elevated after benzyl‐GalNAc treatment, as revealed by the binding ofVicia villosaagglutinin B4andDolichos biflorusagglutinin. Adhesion of treated P815 cells to this lectin immobilized on plastic surfaces also increased. Furthermore, the binding of P815 cells to macrophage‐like RAW 264.7 cells and to peritoneal macrophages also increased after the same treatment. We concluded that elevated levels of cell surface terminal GalNAc in mucin‐type carbohydrate chains increased accessibility of P815 cells to macrophages through Gal/GalNAc‐specific calcium‐dependent lectins.J. Leukoc. Biol. 57: 407–414; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.407

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractOxidants generated by the NADPH oxidase of activated neutrophils can react with a number of tissue targets to form toxic metabolites such as 4‐hydroxynonenal (4‐HNE). 4‐HNE is a lipid peroxidation product generated by free radical attack onω‐6 polyunsaturated fatty acids and is a marker for membrane lipid peroxidation. In this study, we examined the accumulation of 4‐HNE‐protein adducts in phagosomes of neutrophils obtained from a male patient with homozygous X‐linked, flavocytochromeb‐deficient chronic granulomatous disease (CGD), his heterozygous mother, and his normal father. Specific polyclonal antibodies recognizing 4‐HNE‐protein adducts and gp91‐phox(flavocytochromeblarge subunit) were prepared and used to immunocytochemically detect these antigens in cryofixed, molecular distillation‐dried neutrophils. No 4‐HNE‐protein adducts were detected in flavocytochromeb‐deficient cells from the homozygous patient or from the heterozygous CGD carrier. However, in gp91‐phox‐positive cells from both the normal and heterozygous CGD carrier, significant 4‐HNE‐protein adduct labeling was observed, primarily in the phagosomes. When data from single‐ and doublelabeled cells were combined, the frequency distribution of the labels in phagosomes supported this observation, showing that neutrophils from the heterozygous CGD carrier were 71% 4‐HNE‐protein adduct‐positive and 56% gp91‐phox‐positive, while cells from the normal father were>97% positive for both 4‐HNE‐protein adducts and gp91‐phox. These results confirmed the nitroblue tetrazolium tests of 100%, 60 ± 2%, and 0% positive for the father's, mother's, and son's cells, respectively, and demonstrated that 4‐HNE‐protein adduct antibodies are useful and accurate probes of the occurrence of lipid peroxidation in vivo. We conclude that 4‐HNE and resulting 4‐HNE‐protein adducts are generated as a result of NADPH oxidase activity in the phagosomes of human neutrophils and that these lipid peroxidation products may contribute to microbial killing and/or damage of neutrophil phagolysosomal proteins.J. Leukoc. Biol. 57: 415–421; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.3.415

出版商:Wiley    

年代:1995

数据来源: WILEY