Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.     

Reduced intracellular oxidative metabolism promotes firm adhesion of human polymorphonuclear leukocytes to vascular endothelium under flow conditions

The interaction of polymorphonuclear leukocytes (PMN) with the vascular endothelium and their subsequent extravasation to the tissues is a key step during different physiological and pathological processes. In certain of these pathologies the oxygen tension becomes very low, leading to reduced cellular oxidative status. To evaluate the effect of lowering the intracellular redox status in the interaction of PMN with the endothelium, exposure to hypoxic conditions as well as treatment with different antioxidant agents was carried out. PMN exposure to hypoxia enhanced β₂ integrin-dependent adhesion to intercellular adhesion molecule-1-coated surfaces, concomitant with a decrease in the intracellular redox status of the cell. As occurs with hypoxia, treatment with antioxidants produced a decrease in the oxidation state of PMN. These agents enhanced adhesion of PMN to human umbilical vein endothelial cells stimulated with tumor necrosis factor-α (TNF-α), and this effect was also mediated by β₂ integrins LFA-1 and Mac-1. Adhesion studies under defined laminar flow conditions showed that the antioxidant treatment induced an enhanced adhesion mediated by β₂ integrins with a decrease in the fraction of PMN rolling on TNF-α-activated endothelial cells. The up-regulated PMN adhesion was correlated to an increase in the expression and activation of integrin Mac-1, without loss of L-selectin surface expression. Altogether, these results demonstrate that a reduction in the intracellular oxidative state produces an enhanced β₂ integrin-dependent adhesion of PMN to stimulated endothelial cells under conditions of flow.     

Effect of Ebselen on polymorphonuclear leukocyte adhesion to and migration through cytokine-activated vascular endothelium.

Ebselen (PZ51, 2-Phenyl-1, 2-Benzoisoselenazol-3-(2H)-one) is a selinyl organic compound with anti-inflammatory properties. Some of its pharmacological effects are thought to result from its peroxidase activity. Here we examined the effects of Ebselen on polymorphonuclear leukocyte (PMNL) adhesion to umbilical vein endothelium and transendothelial migration in a modified Boyden chamber in which both PMNL-dependent and endothelial-dependent (IL-1, TNF alpha) PMNL adhesion and migration can be measured. Ebselen was found to dose dependently inhibit the adhesion of PMNL to IL-1 activated endothelium and to inhibit transendothelial PMNL migration induced by IL-1 alpha, and TNF alpha with an IC50 value of 28 microM. Transendothelial migration induced by the PMNL chemotactic agents C5adesArg and N-formyl-norleu-leu-phe was also inhibited at slightly higher concentrations. The effect of Ebselen was not on endothelial cell activation but on PMNL activation for adhesion and migration. This effect on PMNL was irreversible for the duration of the assay period (75 min). The results suggest that the anti-inflammatory activity of Ebselen may, in part, be due to direct inhibition of PMNL adhesion to vascular endothelium and transendothelial migration in response to a variety of inflammatory mediators.     

Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion.

Interleukin-1 (IL-1), an inflammatory/immune mediator, acts directly and selectively on cultured human vascular endothelial cells to alter two important functional properties. First, IL-1 induces endothelial cell biosynthesis and surface expression of a tissue factor-like procoagulant activity. Second, IL-1 dramatically increases the adhesiveness of the endothelial cell surface for human peripheral blood polymorphonuclear leukocytes (6-42-fold increase) and monocytes (2-5-fold increase), as well as the related leukocyte cell lines HL-60 and U937. These IL-1 effects are concentration-dependent (maximum, 5-10 U/ml), time-dependent (peak 4-6 hours), and reversible. Cycloheximide and actinomycin D block these IL-1 actions on endothelium, which suggests the requirement for de novo protein synthesis. Human-monocyte-derived IL-1, cell-line--derived IL-1, and recombinant IL-1 exhibited comparable biologic activities in our assays, whereas two other mediators, IL-2 and immune interferon, were without effect. IL-1 stimulated procoagulant activity and leukocyte adhesion in human endothelial cells cultured from both umbilical veins and adult saphenous veins but not in other cultured cell types, including SV-40-transformed human endothelial cells and human dermal fibroblasts. Similar actions of IL-1 on vascular endothelium in vivo may contribute to the development of intravascular coagulation and enhanced leukocyte--vessel wall adhesion at sites of inflammation.     

Effect of platelet-activating factor on leukocyte adhesion to microvascular endothelium

The hamster cheek pouch microcirculation was used to investigate the effects of platelet-activating factor (PAF) on leukocyte adhesion to microvascular walls by means of intravital microscopy. PAF was applied topically at concentrations ranging from 10^–11 to 10^–5 M. An inverse relationship between PAF concentration and number of adhering white cells per 100-m length was found in venules ranging in diameter from 10 to 60 m (grouped into 10-m intervals). Importantly, the PAF-induced adhesion of leukocytes lasted for the 3-h experimental period. We postulate that induction of leukocyte adhesion to venular endothelium is an important role of PAF in inflammatory processes.     

Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain.

Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.     

Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells.

Perivasculitis and endothelial cell abnormalities are characteristic histopathologic features of syphilis, a sexually transmitted disease caused by Treponema pallidum. To extend earlier studies demonstrating that T. pallidum activates endothelial cells, we now show that virulent T. pallidum, but not heat-killed T. pallidum or nonpathogenic Treponema phagedenis, promotes increased adherence of lymphocytes and monocytes to human umbilical vein endothelial cells. Lymphocytes and monocytes are the two cell types prominent in the histopathology of syphilis. Recognition that T. pallidum can stimulate endothelial cells to bind leukocytes provides important insights into the early mechanisms of syphilis immunopathogenesis.     

Tumor cell-endothelial interactions. Increased adhesion of human melanoma cells to activated vascular endothelium.

The authors examined the adhesion of seven human melanoma cell lines to cultured human umbilical vein endothelial cells (HEC) that were activated by cytokines or bacterial endotoxin. The adhesion of Hs 294T and MEL-24 cells was markedly increased (approximately 2 to 12-fold) after pretreatment of HEC monolayers for 6 hours with tumor necrosis factor, interleukin-1, or endotoxin. Smaller increases were noted with the cell lines RPMI 7951, HT 144, Malme-3M, MEL-2, and no significant increase was observed with MEL-5. Cytokine and endotoxin effects on melanoma-HEC adhesion were concentration- and time-dependent, with onset by 2 hours, peak at 6-8 hours and maintenance through 48 hours. Cytokine induction of increased HEC adhesiveness for melanoma cells was blocked by actinomycin-D or cycloheximide, suggesting the requirement for RNA and protein synthesis. Interaction of melanoma cells with subendothelial matrix did not appear to play a primary role because: 1) phase contrast and electron microscopy revealed direct contact between tumor cells and endothelial cells in standardized monolayer adhesion assays; 2) increased adhesion (rosette formation) of tumor cells to activated HEC was also observed after nonenzymatic resuspension of HEC, and 3) the matrix peptide GRGDSP partially blocked (approximately 45%) Hs 294T cell adhesion to subendothelial matrix, but had little or no effect on adhesion to activated HEC monolayers. Taken together, these data suggest that inducible HEC surface changes may mediate the adhesion of certain melanoma cells, thereby exerting an active influence over the metastatic process.     

The effect of prostacyclin on the adhesion of leucocytes to injured vascular endothelium

The effect of local application of various solutions on leucocyte adherence to the wall of small blood vessels in the microcirculation of the rat mesentery was examined. Leucocyte adhesion was produced by local application of zymosan-activated complement. Solutions of EDTA, lignocaine and prostacyclin when applied locally cause the release of a high proportion of leucocytes previously firmly adherent to the endothelium of venules and small veins without producing any significant change in the rate of blood flow through the affected vessels. Acetylcholine injected intravenously increases the rate of blood flow through the mesenteric microcirculation several fold but has no apparent effect on pre-existing leucocyte sticking. The findings suggest that in normal small blood vessels production of prostacyclin by vascular endothelium may inhibit adhesion of leucocytes to the vascular wall. When endothelium is injured local production of prostacyclin may be inhibited sufficiently to permit adhesion of leucocytes to the injured endothelium and so induce the earliest stage in the emigration of leucocytes into the area of injury. Lignocaine may possibly inhibit leucocyte sticking by increasing local production of prostacyclin, but the mode of action of EDTA and many other aspects of the mechanism responsible for leucocyte sticking remain obscure.     

Benoxaprofen inhibits the adhesion of human monocytes to cultured vascular endothelium

Pretreatment of human monocytes with benoxaprofen for at least 2 h produced a dose-dependent abrogation of their adhesion to monolayers of cultured porcine endothelium with 0.05 g/ml and 50.0 g/ml of the drug inducing a mean 33% and 83% inhibition of adhesion respectively. When the endothelium was treated with the drug there was no modification of monocyte adhesion. In contrast, pretreatment of endothelium with 5.0 and 50.0 g/ml benoxaprofen for at least 6 h, resulted in a mean 35% and 31% inhibition of polymorphonuclear cell (PMN) adhesion in 6/11 experiments. This inhibitory effect was not seen when drug-treated PMNs were added to endothelium. An impairment of monocyte chemotactic migration was only apparent with high concentrations of the drug (50 g/ml). These results suggest that an important anti-inflammatory property of benoxaprofen is the inhibition of monocyte adhesion to vascular endothelium.     

Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo

Background

There is strong evidence implicating eosinophils in host defence against parasites as well as allergic disease pathologies. However, a lack of reagents such as monoclonal antibodies (mAbs) specific for eosinophils has made it difficult to confirm the functional role of eosinophils in such disease conditions. Using an established mammary model of allergic inflammation in sheep, large numbers of inflammatory cells enriched for eosinophils were collected from parasite-stimulated mammary glands and used for the generation of mAbs against ovine eosinophils.

Results

A panel of mAbs was raised against ovine eosinophils of which two were shown to be highly specific for eosinophils. The reactivity of mAbs 3.252 and 1.2 identified eosinophils from various cell and tissue preparations with no detectable reactivity on cells of myeloid or lymphoid lineage, tissue mast cells, dendritic cells, epithelial cells or other connective tissues. Two other mAbs generated in this study (mAbs 4.4 and 4.10) were found to have reactivity for both eosinophils and neutrophils.

Conclusion

This study describes the production of new reagents to identify eosinophils (as well as granulocytes) in sheep that will be useful in studying the role of eosinophils in disease pathologies in parasite and allergy models.     

Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide.

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels greater than 25 microns, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a 'metabolic' factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions.

Because the mechanisms associated with recruitment of monocytes to brain in AIDS encephalitis are unknown, we used tissues from rhesus monkeys infected with simian immunodeficiency virus (SIV) to examine the relative contributions of various adhesion pathways in mediating monocyte adhesion to endothelium from encephalitic brain. Using a modified Stamper and Woodruff tissue adhesion assay, we found that the human monocytic cell lines, THP-1 and U937, and the B cell line, Ramos, preferentially bound to brain vessels from monkeys with AIDS encephalitis. Using a combined tissue adhesion/immunohistochemistry approach, these cells only bound to vessels expressing vascular cell adhesion molecule-1 (VCAM-1). Furthermore, pretreatment of tissues with antibodies to VCAM-1 or cell lines with antibodies to VLA-4 (CD49d) inhibited adhesion by more than 70%. Intercellular adhesion molecule-1 (ICAM-1)/beta 2 integrin interactions were not significant in mediating cell adhesion to the vasculature in encephalitic simian brain using a cell line (JY) capable of binding rhesus monkey ICAM-1. In addition, selectin-mediated interactions did not significantly contribute to cell binding to encephalitic brain as there was no immunohistochemical expression of E-selectin and P-selectin in either normal or encephalitic brain, nor was there a demonstrable adhesive effect from L-selectin using L-selectin-transfected 300.19 cells on simian encephalitic brain. These results demonstrate that using the tissue adhesion assay, THP-1, U937, and Ramos cells bind to vessels in brain from animals with AIDS encephalitis using VCAM-1/alpha 4 beta 1 integrin interactions and suggest that VCAM-1 and VLA-4 may be integral for monocyte recruitment to the central nervous system during the development of AIDS encephalitis.     

In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry

An in vivo mouse cage implant system was used to determine whether leukocyte cytokine mRNA responses to implanted biomaterials were dependent on surface chemistry. Surfaces displaying various chemistries (hydrophobic, hydrophilic, anionic, and cationic) were placed into stainless steel cages and implanted subcutaneously. Semiquantitative RT-PCR analyses revealed that hydrophilic surfaces showed a decreased expression of proinflammatory cytokines, IL-6 and IL-8, and pro-wound healing cytokines, IL-10 and TGF-beta by adherent cells, and mRNA levels of the proinflammatory cytokine, IL-1beta, and the pro-wound healing cytokine IL-13 were decreased in surrounding, exudate cells. Cytokine responses by adherent and exudate cells to hydrophobic, anionic and cationic surfaces were similar and indicative of a strong inflammatory response at the earliest time point followed by a wound healing response at later time points. However, no differences in the types or levels of exudate cells for any of the surfaces or the empty cage at each of the respective time points were observed, indicating their respective biocompatibility. These studies identify hydrophilic surface chemistries as having significant effects on leukocyte cytokine responses in vivo by decreasing the expression of inflammatory and wound healing cytokines by inflammatory cells adherent to the biomaterial as well as present in the surrounding exudate.     

L- and P-selectins collaborate to support leukocyte rolling in vivo when high-affinity P-selectin-P-selectin glycoprotein ligand-1 interaction is inhibited

P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin controls early leukocyte rolling during inflammation. Interestingly, antibodies and pharmacological inhibitors (eg, rPSGL-Ig) that target the N-terminus of PSGL-1 reduce but do not abolish P-selectin-dependent leukocyte rolling in vivo whereas PSGL-1-deficient mice have almost no P-selectin-dependent rolling. We have investigated mechanisms of P-selectin-dependent, PSGL-1-independent rolling using intravital microscopy. Initially we used fluorescent microspheres to study the potential of L-selectin and the minimal selectin ligand sialyl Lewis(x) (sLe(x)) to interact with postcapillary venules in the absence of PSGL-1. Microspheres coated with combinations of L-selectin and sLe(x) interacted with surgically stimulated cremaster venules in a P-selectin-dependent manner. Microspheres coated with either L-selectin or sLe(x) alone showed less evidence of interaction. We also investigated leukocyte rolling in the presence of PSGL-1 antibody or inhibitor (rPSGL-Ig), both of which partially inhibited P-selectin-dependent leukocyte rolling. Residual rolling was substantially inhibited by L-selectin-blocking antibody or a previously described sLe(x) mimetic (CGP69669A). Together these data suggest that leukocytes can continue to roll in the absence of optimal P-selectin/PSGL-1 interaction using an alternative mechanism that involves P-selectin-, L-selectin-, and sLe(x)-bearing ligands.     

Reduction in cellular and vascular rejection by blocking leukocyte adhesion molecule receptors.

Whether antibody blockage of leukocyte receptors for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 would prevent cardiac graft rejection was studied in a rabbit heterotopic transplant model. Monoclonal antibody 60.3, anti-CD18 (intercellular adhesion molecule-1 receptor, Group 1, n = 10) and monoclonal antibody HP1/2, anti-VLA-alpha 4 (vascular cell adhesion molecule-1 receptor, Group 2, n = 10) were administered to transplanted unimmunosuppressed animals. At 7 days, donor heart histology was compared to transplanted untreated controls (Group 3, n = 11). Peripheral white blood cell counts on postoperative day 2 were significantly higher in both treatment groups than controls. Significant increases in circulating neutrophils occurred in Group 1 (P < or = 0.05); lymphocytes predominated in Group 2 (P < or = 0.05). A significant reduction in cellular rejection was seen in Group 1 (P < or = 0.05) but not Group 2 hearts. Group 1 hearts demonstrated localization of lymphocytes to perivenular collections, whereas Group 2 hearts evidenced diffuse interstitial infiltration. Both treatment groups demonstrated a reduction in transplant arteritis compared to controls. Results suggest that monoclonal antibody 60.3 (anti-CD18) may hold promise as a therapeutic agent for both cellular and vascular rejection. Monoclonal antibody HP1/2 (anti-VLA-alpha 4) may reduce vascular rejection disproportionate to cellular rejection.     

In vivo rolling and endothelial selectin binding of mononuclear leukocytes is distinct from that of polymorphonuclear cells

In inflammation, rolling of leukocytes along the microvascular endothelium is a precondition for subsequent integrin-mediated firm adhesion and extravasation. Rolling characteristics of polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL) in small venules (15–25 μm) of the rat mesentery were studied by intravital fluorescence microscopy under basal conditions and after intravenous treatment with an anti-rat neutrophil serum (ANS). The baseline rolling fraction of the venular total leukocyte flux was 36 ± 15% (mean ± SD). The PMNL fraction of the systemic leukocyte count was 27 ± 9%. Treatment with ANS resulted in total depletion of circulating PMNL and reduced the leukocyte rolling fraction to 12 ± 5%, in this situation represented only by MNL. In rats treated intraperitoneally with interleukin (IL)-1β for 4 h, the leukocyte rolling fraction was 53 ± 13% and was reduced to 33 ± 11% after ANS treatment. These data indicated that most, if not all, circulating PMNL rolled along the venular endothelial lining in the rat mesentery prepared for intravital microscopy, whereas MNL rolling was minor (～ 10%) under the same basal condition. In cytokine-activated tissue, on the other hand, the number of rolling MNL was greatly increased. While PMNL rolling is known to be entirely selectin dependent, the increased MNL rolling after IL-1 stimulation was likely mediated by α₄ integrins, inasmuch as the rolling fraction of isolated peripheral blood lymphocytes injected into the microcirculation of the cytokine-stimulated mesentery was reduced from 31 ± 14% to 6 ± 2% by pre-treatment of the cells with a monoclonal antibody against the rat integrin α₄ chain. In accordance with the in vivo rolling characteristics of the two cell populations, binding of soluble P- or E-selectin (selectin/IgG chimeras) was less intense for blood lymphocytes than for granulocytes, as determined by flow cytometric analyses of rat and human leukocytes. Taken together, our findings in vivo indicate that the adhesive interactions responsible for rolling of PMNL and MNL, respectively, are distinct in terms of receptor occupancy, and may help explain the temporal selectivity in recruitment of different leukocyte subpopulations in inflammatory or immune reactions.     

Human blood dendritic cells: binding to vascular endothelium and expression of adhesion molecules

To investigate the binding properties of dendritic cells (DC) to vascular endothelium, a comparative analysis was undertaken of DC, monocytes and lymphocytes isolated from the blood of 25 healthy subjects using monolayers of human umbilical vein endothelial cells as the adherence substrate. More blood DC (mean 24% adherence) were adherent to endothelial monolayers than monocytes (mean 18%; P < 0.001) and lymphocytes (mean 12%; P < 0.001). When the monolayers were pretreated with tumour necrosis factor-alpha (TNF-α) all leucocyte populations exhibited an increased attachment, but there was still greater binding of DC (mean 37% adherence) in comparison with monocytes (mean 23%; P < 0.001) and lymphocytes (mean 18%; P < 0.001). Flow cytometric analysis revealed that in relation to monocytes and lymphocytes the DC had a higher surface expression of the adhesion molecules CD11a (P < 0.05), CD11c (P < 0.05) and CD54 (P < 0.05) but a lower prevalence of cells bearing CD49d (mean 38%; P < 0.05) and the homing receptor CD62L (mean 14%; P < 0.001). CD1a was present on 22% of DC and virtually absent from the surface of monocytes and lymphocytes. The intensity of expression of the β₁-integrins, CD49c, CD49d and CD49e was greater on DC than lymphocytes and monocytes (P < 0.05). Antibody blocking studies demonstrated that DC binding to untreated and TNF-α-treated endothelium was dependent upon the expression of CD11a, CD18 and CD49d, and the simultaneous application of anti-CD18 and anti-CD49d antibodies produced an approximate 70% inhibition of adhesion (P < 0.001). Thus, the expression of both β₁- and β₂-integrins contributes to the adhesive interaction between DC and endothelium.     

牛磺酸镁配合物保护血管内皮改善血流变学的实验研究

目的:探讨牛磺酸镁配合物保护血管内皮和改善血流变的作用。方法:冰浴加肾上腺素复制整体血管内皮损伤模型,检测血液循环内皮细胞(CEC)数量和血流变学变化,观察牛磺酸镁配合物的作用。结果:模型大鼠,CEC数量明显增加;全血比粘度增高,血液粘稠度增大,红细胞压积增大,红细胞变形能力下降,聚集能力增高;同时,血浆内皮素水平增高,一氧化氮代谢产物减少,一氧化氮合酶活性亦下降。牛磺酸镁配合物能减少模型大鼠的CEC数量;降低模型大鼠全血粘度的低切和高切变率,减少红细胞压积,提高红细胞变形能力;血浆内皮素水平下降、一氧化氮代谢产物增多、一氧化氮合酶活性增高。上述作用均呈剂量依赖性。结论:冰浴加肾上腺素法可作为整体条件下评价血管内皮损伤的模型,牛磺酸镁配合物具有血管内皮保护和血流变改善作用。