摘要:

AbstractInterleukin‐7 (IL‐7) was originally discovered to be a pre‐B cell growth factor. Soon thereafter, a broader role for IL‐7 in leukocyte development and function began to be identified. IL‐7 now has been shown to be a critical cytokine for normal T and B lymphopoiesis and a mobilizer of pluripotent stem cells and myeloid progenitors. IL‐7 has been demonstrated to enhance T cell function and induce cytokine expression in monocytes. Preclinical studies have already found that IL‐7 could accelerate murine lymphocyte regeneration following chemotherapy and bone marrow transplantation, induce anti‐tumor effects in mice, and expand anti‐HIV‐specific human T cells. Thus it is essential that further preclinical and clinical research be performed to evaluate IL‐7 as a potential therapy for leukopenia, bone marrow/stem cell transplantation, cancer, and HIV/AIDS.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.623

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractGranulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is a naturally occurring growth factor produced by several cell types in response to a variety of stimuli. GM‐CSF has potent stimulatory effects on the growth and maturation of hematopoietic cells and has profound effects on mature circulating effector cells. Clinical applications of GM‐CSF include ameliorating chemotherapy‐induced neutropenia and enhancing hematopoietic recovery after bone marrow transplantation. This review evaluates the effect of GM‐CSF on myeloid cells and its clinical applications.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.634

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe production of nitric oxide (NO) and its role in the anti‐tumor and anti‐microbial effects of rodent macrophages appears well established. In contrast, the circumstances required for its release from human monocytes/macrophages and its potential role in human pathology remain controversial. Evidence to be discussed suggests that NO is a redundant, autotoxic, immunosuppressive, and inefficient mediator of macrophage function. For these reasons, the expression of nitric oxide synthase as a rapid‐response, high‐output effector pathway may have been evolved out of the human monocyte/macrophage response repertoire or severely restricted in its expression. Hypothetical roles for a modest and circumscribed production of NO by human macrophages are proposed.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.643

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have previously shown that the calcium‐binding protein complex, calprotectin, purified from rat inflammatory peritoneal cells exerts marked cytotoxic activity against rat, mouse, and human tumor cells. We studied here whether the cytotoxicity is caused by induction of apoptosis, using mouse EL‐4 lymphoma and human MOLT‐4 leukemia lines as targets. The rat calprotectin sample inhibited [3H]thymidine incorporation into these cells by partially 24 h and almost completely in 48 h of culture at concentrations of 100–200 μg/ml. Morphological changes, that is, loss of cell volume and nuclear condensation and/or fragmentation, appeared in both cell types cultured with calprotectin from 20 h, and such apoptotic cells subsequently increased in number to compose the great majority of the cells at 40 h. Cell death, measured by stainability with trypan blue, lagged behind the emergence of the apoptotic morphology by about 2 and 10 h in EL‐4 and MOLT‐4 cells, respectively. DNA fragmentation was observed in EL‐4 cells cultured with calprotectin, whereas it was not observed in MOLT‐4 cells, consistent with results of flow cytometry showing that loss of cell DNA content caused by the factor was greater in EL‐4 cells. The data indicate that calprotectin induces the apoptosis of certain tumor cells but that the occurrence of DNA fragmentation is dependent on cell type. Finally, the apoptosis‐inducing activity of the calprotectin sample was abrogated by the presence of 10 μM zinc, whereas it was not affected by 5 mM calcium or magnesium.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.650

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe nucleus of the mature human neutrophil is segmented into three to five interconnected lobes. The physiological purpose of this segmentation is unknown, as is the mechanism by which the lobes are formed during differentiation. Using video observation of migrating human neutrophils simultaneously illuminated for fluorescence and phase‐contrast microscopy, we analyzed nuclear movements with respect to cell shape changes. The number of nuclear lobes and their relative size remained constant during observation (up to 1 h). The thin connecting segments between the lobes elongated and attenuated extensively but never separated. Electron microscopic analysis of neutrophil nuclei revealed no specialized nuclear or cytoplasmic structures in the vicinity of connecting segments. With fluorescence in situ hybridization of whole chromosome probes, we determined that chromosomes are randomly distributed among neutrophil nuclear lobes. HL60 cells are a human myelocytic line that, with retinoic acid treatment, segment their nuclei and differentiate into neutrophil‐like cells over several days. Using a rapidly responding variant line termed HL60/S4 (Cancer Res.52, 949–954), we found that segmentation could be induced within 24 h. We tested the role of cytoskeletal elements in the process of nuclear segmentation. Neither the microtubule inhibitor nocodazole nor the microfilament inhibitor cytochalasin D prevented nuclear segmentation. Together, our studies suggest that nuclear lobes in neutrophils are relatively stable structures that are not generated by microtubule‐ or microfilament‐dependent forces.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.659

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractTaurine (Tau) is an exceptionally abundant free amino acid in the cytosol of inflammatory cells and especially in neutrophils. Taurine protects cells from self‐destruction during processes that generate oxidants. The major function of Tau in leukocytes is to trap chlorinated oxidants (HOCl). Taurine reacts with HOCl to produce the long‐lived compound taurine chloramine (TauCl). Previously, we have shown that other products of the neutrophil chlorinating system are able to modify functions of macrophages. In this study, we investigated in vitro the influence of TauCl on the generation of inflammatory mediators by activated macrophages. We have found that TauCl inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor α, and interleukin‐6, but TauCl slightly enhanced the release of IL‐1α. The formation of nitrites by interferon‐γ‐activated macrophages was inhibited by TauCl in a dose‐dependent manner. Taurine chloramine also reduced the level of inducible nitric oxide synthase (iNOS) mRNA in macrophages, in a similar concentration‐dependent manner. Although our experiments do not exclude a direct effect of TauCl on enzymatic activity of iNOS, the inhibition of iNOS expression seems to be the major mechanism responsible for suppression of NO formation. Finally, we discuss the biological role of TauCl in vivo. We suggest that at the site of inflammation TauCl works as a specific signaling molecule of activated neutrophils that coordinates the generation of inflammatory mediators in macrophages.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.667

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWhen incubated with lipopolysaccharide (LPS) in the presence of plasma, neutrophils become primed for enhanced release of superoxide in response to triggering by formyl‐Met‐Leu‐Phe (fMLP). The effect of LPS on phagocytes is inhibited by a synthetic lipid A precursor, LA‐14‐PP (lipid IVa) or by LPS fromRhodobacter sphaeroides(Rs). We studied the mechanisms by which LA‐14‐PP orRs‐LPS inhibited LPS‐induced responses. When neutrophils were exposed to LA‐14‐PP orRs‐LPS for 3 min and then toEscherichia coli‐LPS, the antagonists inhibited priming for superoxide release, and also blocked up‐regulation of CD11b and adherence. This inhibition was dependent on plasma, was not overcome by higher amounts ofE. coli‐LPS or plasma, and was not observed at 0°C, suggesting thatE. coli‐LPS was not able to interact with its receptor or other cellular recognition molecule in neutrophils that had been exposed to the antagonists. The alternative possibility that LA‐14‐PP orRs‐LPS depleted a plasma cofactor, resulting in inhibition of priming, was investigated by using LPS fromPorphyromonas gingivalis(Pg) andBordetella pertussis(Bp). These LPS primed neutrophils in a plasma‐dependent and CD14‐dependent manner, but were not blocked by LA‐14‐PP orRs‐LPS. When sub‐optimal concentrations of plasma were exposed to LA‐14‐PP orRs‐LPS, and then mixed withPg‐IPS orBp‐LPS, followed by incubation with neutrophils, priming and up‐regulation of GD11b were inhibited, and this inhibition was overcome by increasing the concentration of plasma. Binding of LPS‐binding protein (LBP) in plasma to immobilizedE. coli‐LPS was inhibited by pre‐incubation of plasma with LA‐14‐PP or Rs‐LPS. Together with the result that treatment of plasma with anti‐LBP antibody abolished the cofactor activity of plasma, these results indicated that LA‐14‐PP andRs‐LPS depleted LBP from plasma, resulting in inability of LPS to act on neutrophils. Thus LA‐14‐PP andRs‐LPS inhibited the action of LPS on neutrophils by at least two mechanisms, blocking of LPS receptor recognition and depletion of the cofactor LBP.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.675

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractTo investigate whether the CD30 molecule, expressed only by a minority of T and B cells, defines a subtype of T helper cells,Pityrosporum orbiculare‐specific CD4+T cell clones were assessed for CD30 protein and gene expression. The clones were defined as Th1, Th0, and Th2 according to their cytokine mRNA profile detected by reverse transcription PCR (RT‐PCR). The kinetics of CD30 expression after OKT3 (anti‐CD3) stimulation was analyzed by flow cytometry, immunocytochemistry, and RT‐PCR. OKT3 activation induced a high expression of CD30 in cells of both Th1 and Th0 as well as Th2 type after 1‐3 days. A difference between the clones was noted in that the Th2 clones remained highly positive in CD30 expression, whereas expression in the other clones started to decline from day 3. These data indicate that CD30 is expressed in activated CD4+ T cells of all three subtypes, and that the expression is sustained in Th2 cells.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.683

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractAdhesion is known to prime neutrophils for physiological activation in response to cytokines and other stimuli. We have employed the technique of receptor cross‐linking to study the potential role of CD18, the common β‐subunit of the β2‐integrin family of adhesion molecules, in the regulation of the respiratory burst, as measured by luminol‐enhanced chemiluminescence and iodination, in human neutrophils. CD18 cross‐linking primed neutrophils to activate the respiratory burst after stimulation with tumor necrosis factor α (TNF‐α) (100 units/mL), formyl‐methionyl‐leucyl‐phenylalanine (fMLP) (1 μM), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) (1 μg/mL), but not granulocyte colony‐stimulating factor (G‐CSF) (1 μg/mL), interferon‐γ (IFN‐γ) (100 U/mL), or phorbol myristate acetate (100 nM). The maximal rate of chemiluminescence induced by fMLP, TNF‐α, and GM‐CSF was enhanced 8‐, 6‐, and 1.5‐fold, respectively, following CD18 cross‐linking. Priming of the respiratory burst by direct engagement of CD18 was confirmed in neutrophil‐mediated iodination experiments, where iodination induced by TNF‐α, fMLP, and GM‐CSF was increased 15‐, 20‐, and 7‐fold, respectively, by CD18 cross‐linking. Immunoblot experiments demonstrated that TNF‐α‐induced tyrosine phosphorylation was both accelerated and more intense in neutrophils after cross‐linking of CD18. Major tyrosine phosphoprotein products include proteins with approximate molecular masses of 40, 70, and 110 kDa. Genistein (50μM), a selective tyrosine kinase inhibitor, reduced the TNF‐α‐stimulated respiratory burst by>80% whether or not CD18 was cross‐linked. These results affirm the importance of CD18 in adhesion‐dependent priming of neutrophil functions and demonstrate that CD18 engagement per se is sufficient to prime neutrophils for cytokine‐induced signal transduction mediated by tyrosine phosphorylation.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.690

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMurine retrovirus infection induces loss of vitamin E and immune dysfunction with loss of cytokine production by T‐helper cells. Therefore interferon‐γ (IFN‐γ) was given during dietary vitamin E supplementation to effectively prevent murine retrovirus‐induced immunosuppression, cytokine dysregulation, and development of murine AIDS. Administration of IFN‐γ during vitamin E supplementation significantly prevented development of retrovirus‐induced suppression of splenic natural killer cell activity and T cell proliferation. It also significantly slowed retrovirus‐induced elevation of T helper (Th) 2 cytokine [interleukin (IL)‐4, IL‐5, and IL‐10] production and monokine (IL‐6 and tumor necrosis factor‐α) secretion by splenocytes. The treatment also prevented loss of Th1 cytokine (IL‐2 and IFN‐γ) secretion by splenocytes from retrovirus‐infected mice alleviating splenomegaly and hyper‐gammaglobulinemia. The combined therapy had an additive therapeutic impact. It was more effective than IFN‐γ treatment or vitamin E supplementation alone in delaying the development of retrovirus‐induced immunosuppression with its cytokine dysregulation.

ISSN:0741-5400    

DOI:10.1002/jlb.58.6.698

出版商:Wiley    

年代:1995

数据来源: WILEY