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排序方式: 共有442条查询结果,搜索用时 15 毫秒
1.
SDF-1 induces IL-8 production and transendothelial migration of human cord blood-derived mast cells 总被引:3,自引:0,他引:3
Lin TJ Issekutz TB Marshall JS 《International archives of allergy and immunology》2001,124(1-3):142-145
BACKGROUND: Mast cell numbers and expression of chemokines are known to increase in the context of angiogenesis and inflammation, but the mechanisms by which this occurs are not understood. Stromal-derived factor-1 (SDF-1) is an important chemokine in angiogenesis and cell migration. The effects of SDF-1 on human mast cells were examined. METHODS: Expression of the SDF-1 receptor CXC chemokine receptor 4 (CXCR4) on mast cells was examined by RT-PCR and flow cytometry. The ability of labeled cord blood-derived mast cells to migrate across HUVEC monolayers in response to SDF-1 was determined. The cytokine and chemokine responses of cord blood-derived mast cells to SDF-1 treatment over 24 h were examined by ELISA. RESULTS: Cord blood-derived human mast cells expressed the CXCR4 receptor for SDF-1 and migrated across HUVEC monolayers in response to this chemokine. Treatment of cord blood-derived mast cells with SDF-1 did not induce degranulation or the production of several cytokines but did induce a highly selective IL-8 response. CONCLUSION: Human mast cells can both migrate across vascular endothelium and produce the pro-angiogenic chemokine IL-8 in response to SDF-1. These responses may be important in angiogenic processes. 相似文献
2.
Enhanced vascular permeability and haemorrhage-inducing activity of rabbit C5ades arg: probable role of polymorphonuclear leucocyte lysosomes. 总被引:10,自引:2,他引:10
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We previously reported that the injection into rabbit skin of rabbit zymosan-activated plasma (ZAP) induces marked polymorphonuclear leucocyte (PMN) infiltration, a transient increase in vascular permeability (1 hr) and prolonged red blood cells extravasation lasting at least 10 hr. Here we describe the fractionation of ZAP to identify the factor(s) responsible for these effects. On CM Sephadex G-25 chromatography, the majority of the leucocyte-attracting, permeability-enhancing and haemorrhage-inducing activities eluted in the high-salt fractions (0 . 6 M ammonium formate, 1 M NaCl pH 5 . 0), suggesting that this is a very basic molecule(s). Furthermore, the three activities eluted in the same fraction on Sephadex G-100, with an apparent molecular weight of 14,000--17,000 daltons. These observations, and the previously described requirement for C5 in the plasma, suggest that C5ades arg is the active factor. Experiments performed in neutropenic rabbits indicated that PMN are required for both the increase in permeability and red cell extravasation. Ultrastructural studies showed extensive degenerative changes in the infiltrating PMNs evident even in 1--2-hr lesions. These ranged from 'watery' cytoplasm, loss of glycogen and cell membrane to segregation and extensive extracellular release of lysosomes. It is postulated that C5ades arg-induced chemotaxis and metabolic perturbations contribute to this rapid degeneration of the PMNs, and that the release of lysosomes from these cells results in progressive vascular injury. 相似文献
3.
The effect of vasodilator prostaglandins on polymorphonuclear leukocyte infiltration and vascular injury. 总被引:4,自引:8,他引:4
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Some severe acute inflammatory reactions are characterized by polymorphonuclear leukocyte (PMN) infiltration as well as vascular and tissue damage with hemorrhage. Two types of mediators that may be involved in such reactions are chemotactic factors and prostaglandins. The chemotactic factors can induce PMN infiltration, while some types of prostaglandins cause vasodilatation. We reported previously that injection of soluble, nonphagocytosable chemotactic stimuli, zymosan-activated plasma (ZAP), or C5a des Arg into rabbit skin induced PMN-dependent hemorrhage. Here we investigated whether prostaglandins may modulate the rate of PMN infiltration, measured with 51Cr-labeled leukocytes and the degree of hemorrhage, measured with 59Fe-labeled red cells. Prostaglandin (PG) E1 (0.5 microgram) or E2 (1 microgram) increased ZAP-induced PMN accumulation by 81% and hemorrhage by 400%. A similar potentiation by PGE2 was observed when submaximal concentrations of ZAP were injected. Prostaglandin F2 alpha had no such effect. These results indicate that the degree of PMN infiltration of the tissues may be one factor determining the severity of vascular damage. Furthermore, vasodilatory prostaglandins, generated during neutrophilic inflammatory reactions, may enhance chemotactic-factor-mediated PMN infiltration and increase the extent of vascular injury. 相似文献
4.
Effect of cyclic adenosine 3'',5''-monophosphate antagonists on endotoxin-induced inhibition of human neutrophil chemotaxis.
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We reported previously that Escherichia coli endotoxin inhibited human neutrophil chemotaxis toward C5a. This effect of endotoxin was antagonized by anti-inflammatory steroids. We now report that dibutyryl cyclic adenosine 3',5'-monophosphate, prostaglandin E1, isoproterenol, and cholera toxin also antagonize the suppression of chemotaxis by endotoxin. Each compound inhibited the effect of endotoxin in a dose-dependent fashion. To be effective, each compound except cholera toxin had to be present at the time of endotoxin challenge. Furthermore, propranolol blocked the protective effect of isoproterenol against endotoxin but not the protective effect of dibutyrl cyclic adenosine 3',5'-monophosphate or prostaglandin E1. Dibutyryl cyclic guanosine 3',5'-monophosphate, adenosine 5'-monophosphate, phenylephrine, prostaglandin F2 alpha, and carbachol did not modify the suppression of chemotaxis by endotoxin. Anti-inflammatory steroids and dibutyryl cyclic adenosine 3',5'-monophosphate are thought to stabilize phospholipids in certain cell membranes. This phospholipid-stabilizing action may contribute, at least in part, to the protective effect against endotoxin-mediated suppression of neutrophil chemotaxis. 相似文献
5.
Neutrophil migration from blood into inflamed tissues is mediated by adhesion molecules on neutrophils and on vascular endothelium. It was previously shown that the integrins VLA-4 and CD11/CD18 in combination mediate 70-80% of neutrophil recruitment to arthritic joints of rats. To investigate if the remaining recruitment involves the selectins, the effect of adhesion-blocking monoclonal antibodies (mAb) to each of the selectins (E-, P and L-), in combination with mAb to VLA-4 and CD18, on the migration of radiolabeled neutrophils to joints of rats with adjuvant arthritis was examined. Blocking P-selectin inhibited neutrophil accumulation in hindlimb joints by 40% whereas mAb to P- and E-selectin together inhibited the accumulation in all joints by 60% relative to anti-VLA-4 plus anti-CD18 treatment alone. Overall there was 90% inhibition relative to arthritic controls. Blocking E- or L-selectin alone or together had no effect. Our results demonstrate that P-selectin in particular and in concert with E-selectin are required for the VLA-4- and CD18-independent migration of neutrophils to sites of chronic arthritis in the rat. 相似文献
6.
High tidal volume ventilation induces proinflammatory signaling in rat lung endothelium 总被引:9,自引:0,他引:9
Bhattacharya S Sen N Yiming MT Patel R Parthasarathi K Quadri S Issekutz AC Bhattacharya J 《American journal of respiratory cell and molecular biology》2003,28(2):218-224
Alveolar overdistension during mechanical ventilation causes leukocyte sequestration, leading to lung injury. However, underlying endothelial cell (EC) mechanisms are undefined. In a new approach, we exposed isolated blood-perfused rat lungs to high tidal volume ventilation (HV) for 2 h, then obtained fresh lung endothelial cells (FLEC) by immunosorting at 4 degrees C. Immunoblotting experiments indicated that as compared with FLEC derived from lungs ventilated at low volume (LV), HV markedly enhanced tyrosine phosphorylation (TyrP). The tyrosine kinase blocker, genistein, inhibited this response. HV also induced focal adhesion (FA) formation in FLEC, as detected by immunofluorescent aggregates of the alpha(v)beta(3) integrin that co-localized with aggregations of focal adhesion kinase (FAK). Immunoprecipitation and blotting experiments revealed that HV increased TyrP of the FA protein, paxillin. In addition, HV induced a paxillin-associated P-selectin expression on FLEC that was also inhibited by genistein. However, HV did not increase lung water. These results indicate that in HV, EC signaling in situ causes FA formation and induces TyrP-dependent P-selectin expression. These signaling mechanisms may promote leukocyte-mediated responses in HV. 相似文献
7.
TNF- and IL-1 promote leukocyte recruitment to arthritic joints and may contribute to cartilage degradation while regulatory cytokines such as IL-4 and IL-1RA may in part determine the course of arthritis. Here we report the pattern of TNF-, IL-1, IL-6, IFN-, IL-1RA, and IL-4 mRNA expression, detected by RT/PCR, in the talar joint and draining popliteal lymph node (PLN) of rats with adjuvant arthritis (AA). Levels of TNF- and IFN- mRNA were increased in the PLN before clinical signs of arthritis. This was followed by increases in IL-1 and IL-1RA mRNA at d9 and IL-6 mRNA at d12. PLN IL-1RA mRNA levels were positively correlated with those of IL-1 and TNF- throughout d5-d20. IL-4 mRNA levels were highest on days 7 and 20. In the synovium, a small increase in TNF-, IL-1, and IL-6 mRNA was detected on d5 then again on d12. Maximal synovial TNF- levels were reached on d20, while IL-1 peak expression was on d16 and IL-6 on d14. IL-4, IL-1RA, and IFN- mRNA was undetectable in the synovium. Cyclosporin treatment for 4 days, initiated at the height of arthritis, rapidly decreased clinical disease, and decreased migration of neutrophils and T lymphocytes into the joints. Yet no significant effect of CyA was observed on inflammatory cytokine expression, although the correlation between PLN IL-1RA and IL-1 or TNF- was lost in treated animals. Thus there is a variable pattern of cytokine gene expression in rat AA, the undetectable IL-4 and IFN- mRNA in synovium being analogous to human rheumatoid arthritis. 相似文献
8.
Huisman JA; Paulussen RJ; Geurts TB; Odink J; Rekers H 《Human reproduction (Oxford, England)》1997,12(1):34-38
The objective was to demonstrate bioequivalence between s.c. and i.m.
administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio
3:1). In two randomized, single-centre, cross-over studies, 18 healthy
volunteers on each formulation were assigned to one of the two
administration sequences. Subjects were given single doses of one of the
above gonadotrophins after endogenous gonadotrophin production had first
been suppressed using high-dose oral contraceptive. Subsequently, rate
(Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone
(FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax
and AUC, analysis of variance (ANOVA) was performed on log-transformed data
and for tmax ANOVA was performed on ranks. Intramuscular and s.c.
injections of Humegon were bioequivalent with respect to the main
pharmacokinetic parameters, being AUC and Cmax of FSH absorption.
Intramuscular and s.c. injections of Normegon were bioequivalent with
respect to the AUC of FSH and not bioequivalent with respect to the Cmax of
FSH. For tmax of FSH as well as for most LH variables of both preparations,
bioequivalence could not be proven due to the high intra- and
interindividual variability and/or concentrations being close to the
detection limit. Thus, the main pharmacokinetic FSH variables after i.m.
and s.c. administration of Humegon and Normegon were bioequivalent.
相似文献
9.
The effects of the angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on human polymorphonuclear leukocyte (PMNL)-endothelial cell adhesion and transendothelial migration (TEM) were investigated. Stimulation of human umbilical vein endothelial cells by VEGF or bFGF for 18 h up-regulated intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 expression and significantly increased PMNL adhesion and TEM in response to complement fragment 5a (C5a) or interleukin (IL)-8. In contrast, continued exposure to bFGF (24 h-6 days) down-regulated basal and IL-1- or tumor necrosis factor (TNF)-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin expression as well as PMNL adhesion and TEM. These effects could be reversed by introduction of high concentrations of TNF-alpha, C5a, or IL-8. None of these inhibitory effects was observed with VEGF. The acute effects of bFGF and VEGF may facilitate PMNL emigration during acute inflammation, but continued bFGF production may have anti-inflammatory actions during chronic inflammation, angiogenesis, and tumor defense by inhibition of endothelial activation for leukocyte recruitment. 相似文献
10.
Thrombin enhancement of interleukin-1 and tumor necrosis factor-alpha induced polymorphonuclear leukocyte migration. 总被引:3,自引:0,他引:3
W T Drake N N Lopes J W Fenton A C Issekutz 《Laboratory investigation; a journal of technical methods and pathology》1992,67(5):617-627
BACKGROUND: Cytokines such as IL-1 alpha and tumor necrosis factor-alpha (TNF-alpha) activate vascular endothelium to express leukocyte adhesion molecules that promote polymorphonuclear leukocyte (PMNL) migration and to synthesize tissue factor, thus making the endothelium a procoagulant surface. alpha-Thrombin, generated during coagulation, also activates endothelial cells. Since all these processes are likely involved in inflammation, the effect of alpha-thrombin on PMNL interaction with cytokine activated endothelium was investigated. EXPERIMENTAL DESIGN: Human umbilical vein endothelium was grown on polycarbonate filters to investigate the effects interleukin-1 alpha (IL-1 alpha), TNF-alpha, and alpha-thrombin on PMNL transendothelial migration quantitated with 51Cr-labeled PMNL, and on endothelial monolayer permeability, quantitated with 125I-labeled albumin (HSA). To evaluate the expression of endothelial-leukocyte adhesion molecules, enzyme-linked immunosorbent assay was performed on human umbilical vein endothelium monolayers. The effect of thrombin on PMNL accumulation and plasma exudation in inflammation was studied in a rabbit dermal model, using 51Cr-labeled blood leukocytes and [125I]HSA respectively. RESULTS: On resting human umbilical vein endothelium, alpha-thrombin induced a transient increase (2.5- to 4-fold) in monolayer permeability lasting 30 minutes. Slight but significant transendothelial migration of 51Cr-labeled PMNL was induced by alpha-thrombin (7.4 +/- 0.6% of cells added, unstimulated = 1.9 +/- 0.4%), although this response was less than that induced by f-norLeu-Leu-Phe (17%), IL-1 alpha (29%) or TNF-alpha (21%). alpha-Thrombin enhanced the initial rate of IL-1, TNF-alpha and f-norLeu-Leu-Phe induced PMNL transendothelial migration in an additive or supradditive manner (e.g., with IL-1 alpha+alpha-thrombin, migration was 58% greater than additive at 15 to 30 minutes, p < 0.001). Catalytically inactivated alpha-thrombin, D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone and diisopropyl-fluorophosphate alpha-thrombin, did not enhance migration or permeability. In dermal inflammation in rabbits, alpha-thrombin (10 units/site) induced an increase in plasma protein exudation, with only a mild infiltration of PMNL. However, alpha-thrombin synergistically enhanced the PMNL infiltration induced by IL-1 alpha, TNF-alpha, but not that induced by zymosan activated plasma (C5a) or IL-8 (neutrophil-activating peptide-1). These measurements were confirmed histologically. Investigations into the mechanisms of the enhancement of PMNL migration indicated that individually vascular permeability changes, prostaglandins, platelet activating factor, and P-selectin expression did not account for the observation effects. CONCLUSIONS: Alpha-thrombin may have a role in synergistically enhancing PMNL infiltration at sites of inflammation, in part via enzymatic action on the cytokine activated endothelium. The mechanisms involved in this effect are likely a complex interaction. 相似文献