摘要:

AbstractLeukocytes usually pass through the blood stream as nonadherent cells, but during an immune response and inflammation, they become adherent in order to migrate through tissues. Three families of adhesion molecules, the immunoglobulin family, the selectins, and the integrins, participate in interactions between leukocytes and tissues. Near sites of inflammation, leukocytes initially interact with the endothelium via selectins, causing them to slow down and to roll along the walls of blood vessels. Next, chemoattractans induce the activation of integrins on leukocytes. Finally, activated integrins mediate leukocyte migration through the endothelium into the inflamed site. Interactions of leukocytes with other cells and various extracellular matrix (ECM) proteins lead to different functional cell responses, including changes in growth, behavior, and differentiation. Many of these interactions are mediated by integrins, which “integrate” ECM protein signals with the cytoskeleton and which also act as true receptors that generate biochemical signals within the cell. Changes in pH, cytoplasmic Ca2+concentration, phosphorylation, and gene induction have all been observed after integrin engagement. Adhesion‐mediated gene induction in monocytes is perhaps the best example that integrins initiate signaling cascades in the cell to deliver information from the ECM all the way to the nucleus.J. Leukoc. Biol.57: 189–198: 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.189

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractQuinolinic acid (Quin), a metabolite of tryptophan, is a neurotoxin that has been implicated in a variety of neuropathologic disorders that have immune components. The goal of this study was to characterize the changes in the cellular localization of Quin immunoreactivity in a paradigm of immune stimulation with lipopolysaccharide (LPS) in vivo to provide a basis for further studies on the physiological role of Quin in the immune system. Intraperitoneal LPS injection significantly increased Quin immunoreactivity (IR) in lymphoid tissues within 24 h. Spatial changes in splenic Quin‐IR demonstrated a shift from the periarterial lymphoid sheaths to the follicles before returning to control levels by 72 h post‐LPS. The strongly Quin‐IR cells were tentatively identified as interdigitating dendritic cells and macrophages. Only minimal Quin‐IR was detected in liver and lung, even under conditions of LPS stimulation combined with tryptophan loading. These data emphasize the temporally and spatially specific nature of Quin‐IR changes in lymphoid tissues under conditions of immune stimulation and raise the possibility that Quin may have an immunomodulatory function.J. Leukoc. Biol.57: 199–206; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.199

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractRecent studies suggest that heparin, mannose‐6‐phosphate (M6P), and castanospermine (CS) may mediate their anti‐inflammatory effects by inhibiting the passage of leukocytes through the subendothelial basement membrane (BM). In order to test this hypothesis, heparin, M6P, and CS were examined for their ability to prevent the in vitro degradation of a35SO4‐labeled extracellular matrix (ECM) by neutrophils, lymphocytes, endothelial cells (ECs), and platelets, the labeled ECM degradation products being analyzed by gel filtration chromatography. All three compounds inhibited35SO4‐labeled ECM degradation, but M6P and CS were cell‐type specific in their effects. Heparin inhibited the heparanase activity of all cell types examined, confirming the results of previous studies using similar in vitro techniques. M6P selectively inhibited lymphocyte heparanase but not that of platelets, neutrophils, or ECs. CS selectively inhibited phorbol myristate acetate (PMA)‐induced EC heparanase and sulfatase activity but did not affect the constitutive expression of degradative enzymes by non‐stimulated ECs. These findings provide important clues to the mode of action of these compounds and the characteristic inflammatory pathology associated with the use of each anti‐inflammatory agent. In particular, the data support the view that leukocytes markedly differ in the mechanisms they use to degrade BM/ECM to enable extravasation and that some degree of cooperation with EC is required in this process.J. Leukoc. Biol.57: 207–213; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.207

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractTwo populations of IFN‐αproducing cells (IPC) were examined to determine whether they are coordinately dysregulated in human immunodeficiency virus (HIV) disease. IFN‐αproduced in response to herpes simplex virus (HSV) and Sendai virus (SV) was measured and the frequencies of the IPC were obtained by ELISpot assay. IPC that respond to HSV (natural IFN‐αproducing cells) and those responding to SV (predominantly monocytes) were present, on average, at 7.6 and 138 per 104PBMC in healthy controls, respectively. More patients had a reduced IFN‐αresponse to HSV than to SV, and individual patients did not show a decreased response to SV without a decreased response to HSV. Neither IPC function was correlated with CD4+cell levels. We conclude that the defects in IFN‐αproduction in these two cell populations arise independently, possibly due to differences in susceptibility to HIV infection or molecular regulation.J. Leukoc. Biol.57: 214–220; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.214

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractRecombinant MPB64 (rMPB64), a mycobacterial antigen, was obtained from anEscherichia coliclone transformed with a recombinant expression vector, pMAL64c. The rMPB64 was examined for the activity to elicit delayed‐type hypersensitivity (DTH) in guinea pigs injected with liveMycobacterium tuberculosisH37Rv or liveM. bovisBCG Tokyo. It was found that rMPB64 has the same reactivity as native MPB64 (nMPB64) or MPT64 (nMPT64) and the potency to elicit DTH was 13.4 times higher than that of PPD. Because MPB64 is secreted only by livingM. tuberculosisand some strains of BCG, it is possible to use this antigen for the diagnosis of tuberculosis.J. Leukoc. Biol.57: 221–225; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.221

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractGuinea pig peritoneal eosinophils stimulated by platelet‐activating factor (PAF), leukotriene B4(LTB4), and human recombinant C5a (C5a) undergo a rapid concentration‐dependent and partially reversible homotypic aggregation as assessed by changes in light transmission. The phorbol ester phorbol myristate acetate similarly induces a concentration‐dependent aggregation, which is, however, slower in onset, takes longer to reach maximal aggregation, and is irreversible. In addition, we confirmed, using light microscopy, that these agonist‐induced changes in light transmission do indeed represent true homotypic aggregation. We further characterized the aggregation response and showed that there is homologous but little heterologous desensitization when PAF and LTB4are used as stimuli. A requirement for both Ca2+and Mg2+for full manifestation of agonist‐induced aggregation was observed. LTB4‐ and PAF‐induced superoxide anion generation is enhanced by the diacylglycerol kinase inhibitor R59022, whereas aggregation induced by LTB4, but not PAF, is augmented. Lastly, we show that eosinophil aggregation is partially dependent on the adhesion glycoprotein CD18. In summary, therefore, we believe that eosinophil aggregation provides a useful and reliable measure of eosinophil activation.J. Leukoc. Biol.57: 226–234; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.226

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractPhagocytosis and respiratory burst activity were measured by flow cytometry in fresh and cryopreserved human monocytes, after ingestion ofEscherichia coliandStaphylococcus aureus. Mononuclear leukocytes, isolated from 15 healthy donors, were divided into two portions, of which one was examined immediately and the other was cryopreserved for 3 weeks. Morphological characteristics and expression of receptors involved in phagocytosis were similar in fresh and cryopreserved monocytes. Furthermore, both internalization of bacteria and respiratory burst activity remained unchanged after cryopreservation. Transmission electron microscopy confirmed actual internalization of bacteria and not merely bacterial attachment to monocytes. Monocytes were demonstrated to retain integral cellular functions during cryopreservation. This may imply that the method has potential for use in basal and clinical trials.J. Leukoc. Biol.57: 235–241; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.235

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMRL‐lpr/lprmice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). The main characteristics of this disease are increasing autoantibody formation, elevated plasma levels of immune complexes, a massive lymphoproliferation, a rising proteinuria, and arthritic symptoms. Finally, the mice die at an age of about 6 months due to a fatal immune complex glomerulonephritis. Macrophages are involved in the development of SLE due to their functions as antigen‐presenting as well as cytokine‐producing cells. T and B cells are involved in the disease by secreting cytokines and producing antibodies. Pentoxifylline (PTX), a xanthine derivative, is known to exert different effects on functions of leukocytes and erythrocytes and has been used in clinical studies, e.g., in septic shock syndrome. In our studies we first investigated the in vitro effect of PTX on macrophages and lymphocytes derived from MRL‐lpr mice. Our investigations concerning production of superoxide anion and TNF‐αby LPS and/or IFN‐γactivated bone marrow and peritoneal macrophages, MHC class II expression on these cells, and the proliferative capacity and Il‐2 production of mitogen activated lymphocytes, revealed that PTX reduces the activation and the inflammatory response of these cells. Based on these results, we further investigated the effect of in vivo treatment with PTX. MRL‐lpr mice treated with PTX showed diminished proteinuria, reduced titer of dsDNA‐autoantibodies in the plasma and an increased survival rate. Our data clearly demonstrate that PTX is able to diminish the severity of the disease and to prolong the life of MRL‐lpr/lpr mice.J. Leukoc. Biol.57: 242–249; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.242

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractNeutrophil function was examined in rats treated with recombinant human granulocyte colony‐stimulating factor (G‐CSF) using peripheral blood neutrophils (PBNs) and peritoneal exudate neutrophils (PENs) as sources of cells examined in vitro. Adherence to plastic plates containing fetal calf serum of nonstimulated orN‐formylmethionyl‐leucyl‐phenylalanine (fMLP)‐ or tumor necrosis factor‐α‐stimulated PBNs obtained from G‐CSF‐injected rats was lower than that of control rats. In contrast, this adherence was higher in G‐CSF‐treated rats than in the control group when PENs were used. Neutrophil adherence of G‐CSF‐injected and noninjected groups was identical when phorbol myristate acetate was used to stimulate neutrophils. Superoxide production of PBNs stimulated with fMLP in vitro was lower in G‐CSF‐treated rats than in control rats but higher than in the controls when PENs were used. Furthermore, in vitro tumor cell growth inhibition by PBNs was lower in G‐CSF‐treated rats than in control rats, but when PENs were used inhibition was higher than in the controls.J. Leukoc. Biol.57: 250–256; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.250

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractOne of the pathways of metabolism of leukotriene B4(LTB4) and 12‐hydroxy‐5,8,10,14‐eicosatetraenoic acid (12‐HETE) in leukocytes is oxidation of the 12‐hydroxyl group, followed by reduction of the 10,11‐double bond. In the case of 12R‐HETE and 12S‐HETE, this results in the formation of 12‐oxo‐ETE, 10,11‐dihydro‐12‐oxo‐ETE, and the 12Rand 12Sisomers of 10,11‐dihydro‐12‐HETE (i.e., 12R‐HETrE and 12S‐HETrE). We investigated the effects of metabolites of 12‐HETE formed by this pathway on cytosolic calcium levels and chemotaxis in human neutrophils. Of the above series of metabolites, 12S‐HETrE (which has the same absolute stereochemistry at C‐12 as 12R‐HETE) was the most potent in stimulating both cytosolic calcium levels and chemotaxis. It was slightly less potent than 12R‐HETE, consistent with the concept that reduction of the 10,11‐double bond results in a loss of biological activity on neutrophils. The effect of 12S‐HETrE on calcium levels was blocked by preincubation of these cells with LTB4, suggesting that it acted by stimulating the LTB4receptor. 12R‐HETrE was about 20 times less potent than its 12Sisomer in stimulating cytosolic calcium in neutrophils and was also less active as a chemotactic agent. Oxidation of the 12‐hydroxyl group to an oxo group resulted in a further loss of biological activity. 12‐OxoETE, 8‐trans‐12‐oxo‐ETE, and 12‐oxo‐ETrE had only modest effects on cytosolic calcium levels at concentrations as high as 10μM and did not display detectable chemotactic activity. However, 12‐oxo‐ETE and its 8‐transisomer inhibited calcium responses to LTB4by about 40%. It is concluded that reduction of the 10,11‐double bond of 12‐HETE results in a slight loss of biological activity on neutrophils, whereas oxidation of the 12‐hydroxyl group results in a considerably greater loss of activity.J. Leukoc. Biol.57: 257–263; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.2.257

出版商:Wiley    

年代:1995

数据来源: WILEY