Molecular determinants of lipid mediator-induced leukocyte adherence and emigration in rat mesenteric venules

1994 ◽  
Vol 266 (3) ◽  
pp. H847-H853 ◽  
Author(s):  
B. J. Zimmerman ◽  
J. W. Holt ◽  
J. C. Paulson ◽  
D. C. Anderson ◽  
M. Miyasaka ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Platelet Activating Factor ◽  
Leukotriene B4 ◽  
Intercellular Adhesion Molecule ◽  
Lipid Mediator ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Intercellular Adhesion Molecule 1 ◽  
Rolling Velocity ◽  
Molecular Determinants

The objective of this study was to identify the molecular determinants of leukocyte rolling, adherence, and emigration elicited in postcapillary venules by the lipid mediators leukotriene B4 (LTB4) or platelet-activating factor (PAF). Leukocyte-endothelial cell adhesion and shear rate were monitored in rat mesenteric venules during superfusion with either LTB4 or PAF in the presence or absence of monoclonal antibodies (MAbs) directed against either leukocyte (CD18, CD11b) or endothelial cell [intercellular adhesion molecule 1 (ICAM-1), E-selectin, P-selectin] adhesion glycoproteins. In untreated animals and in animals receiving a nonbinding control MAb, LTB4 and PAF increased the number of both adherent (8- and 4-fold, respectively) and emigrated (14- and 8-fold, respectively) leukocytes, while reducing leukocyte rolling velocity (36 and 33%, respectively). The LTB4- and PAF-induced leukocyte adherence and emigration were significantly attenuated by pretreatment with MAbs directed against CD18, CD11b, ICAM-1, and E-selectin, but not P-selectin. The reduction in leukocyte rolling velocity induced by LTB4 was not affected by any of the MAbs; however, both P- and E-selectin MAbs significantly attenuated the reduction in leukocyte rolling velocity elicited by PAF. The results of this study indicate that the leukocyte adherence and emigration induced by both LTB4 and PAF are mediated by CD11b/CD18 on leukocytes and by ICAM-1 and E-selectin on endothelial cells. The molecular determinant of leukocyte rolling appears to be mediator specific, with the selectins mediating the rolling elicited by PAF.

Leukocyte adhesion in local versus hemorrhage-induced ischemia

1992 ◽  
Vol 263 (3) ◽  
pp. H810-H815 ◽  
Author(s):  
M. A. Perry ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Local Ischemia ◽  
Cell Adhesive ◽  
Local Restriction ◽  
Adhesive Interactions

The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.

PECAM-1–dependent neutrophil transmigration is independent of monolayer PECAM-1 signaling or localization

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2816-2825 ◽  
Author(s):  
Christopher D. O'Brien ◽  
Poay Lim ◽  
Jing Sun ◽  
Steven M. Albelda
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Calcium Influx ◽  
Null Model ◽  
Leukotriene B4 ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Border ◽  
Platelet Endothelial Cell Adhesion

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a tyrosine phosphoprotein highly expressed on endothelial cells and leukocytes, is an important component in the regulation of neutrophil transendothelial migration. Engagement of endothelial PECAM-1 activates tyrosine phosphorylation events and evokes prolonged calcium transients, while homophilic engagement of neutrophil PECAM-1 activates leukocyte β-integrins. Although PECAM-1 modulates polymorphoneutrophil transmigration via homophilic PECAM-1–PECAM-1 interaction, the mechanisms underlying endothelial PECAM-1 function are unknown. Proposed mechanisms include (1) formation of a haptotactic gradient that “guides” neutrophils to the cell-cell border, (2) service as a “passive ligand” for neutrophil PECAM-1, ultimately mediating activation of neutrophil β integrins, (3) regulation of endothelial calcium influx, and (4) mediation of SH2 protein association, and/or (5) catenin and non-SH2 protein interaction. Utilizing PECAM-1–null “model” endothelial cells (REN cells), we developed a neutrophil transmigration system to study PECAM-1 mutations that specifically disrupt PECAM-1–dependent signaling and/or PECAM-1 cell localization. We report that interleukin-1β (IL-1β) elicits PECAM-1–dependent transmigration that requires homophilic PECAM–PECAM-1 engagement, but not heterophilic neutrophil PECAM-1 interactions, and is intercellular adhesion molecule-1 dependent. Conversely, whereas IL-8 and leukotriene-B4–mediated transmigration is PECAM-1–independent, PECAM-1 and IL-8–dependent transmigration represent separable and additive components of cytokine-induced transmigration. Surprisingly, neither monolayer PECAM-1–regulated calcium signaling, cell border localization, nor the PECAM-1 cytoplasmic domain was required for monolayer PECAM-1 regulation of neutrophil transmigration. We conclude that monolayer (endothelial cell) PECAM-1 functions as a passive homophilic ligand for neutrophil PECAM-1, which after engagement leads to neutrophil signal transduction, integrin activation, and ultimately transmigration in a stimulus-specific manner.

Phalloidin prevents leukocyte emigration induced by proinflammatory stimuli in rat mesentery

1992 ◽  
Vol 263 (6) ◽  
pp. H1637-H1642 ◽  
Author(s):  
H. Asako ◽  
R. E. Wolf ◽  
D. N. Granger ◽  
R. J. Korthuis
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Mediator ◽  
Control Period ◽  
Leukotriene B4 ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Initial Exposure ◽  
Rolling Velocity ◽  
Rat Mesentery

The objective of this study was to determine whether phalloidin, a potent microfilament stabilizer, can modify inflammatory mediator-induced leukocyte adhesion and extravasation in postcapillary venules of the rat mesentery. To address this issue, the rat mesentery was prepared for in vivo microscopic observation. Venules with initial diameters ranging between 25 and 35 microns were selected for study. Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and the number of adherent (stationary for 30 s) and emigrated leukocytes were initially determined during superfusion of the mesentery with phosphate-buffered saline. After these variables were recorded during the control period, either 100 nM platelet-activating factor (PAF), 20 nM leukotriene B4 (LTB4), or 1 microM N-formyl-methionyl-leucyl-phenylalanine (FMLP) was added to the superfusate. Repeat measurements were obtained between 50 and 60 min after initial exposure to the inflammatory mediator. In some experiments, rats were given phalloidin (25 or 500 micrograms/kg iv) 30 min before superfusion with the inflammatory mediators. Superfusion of the mesentery with either PAF, LTB4, or FMLP enhanced leukocyte adherence and emigration and reduced leukocyte rolling velocity. Pretreatment with the low dose of phalloidin effectively prevented leukocyte emigration but had no effect on the increased leukocyte adherence elicited by the three inflammatory mediators. However, when administered at the higher dose, phalloidin prevented both leukocyte adherence and emigration. Neither dose of phalloidin altered the upregulation of neutrophil membrane CD11/CD18 glycoprotein adherence complex induced by PAF or LTB4. These results are consistent with the concept that PAF, LTB4, and FMLP increase leukocyte extravasation by a process that may involve alterations in the endothelial cell cytoskeleton.

Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and hypercholesterolemic rats

1997 ◽  
Vol 273 (2) ◽  
pp. H854-H860 ◽  
Author(s):  
I. Kurose ◽  
L. W. Argenbright ◽  
D. C. Anderson ◽  
J. Tolley ◽  
M. Miyasaka ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Platelet Aggregation ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Leukocyte Adherence ◽  
Intercellular Adhesion Molecule 1 ◽  
Albumin Leakage ◽  
Endothelial Cell Adhesion

The objective of this study was to define the influence of hypercholesterolemia on ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules. The microvascular alterations normally elicited by I/R (leukocyte adherence and emigration, albumin leakage, and platelet aggregation) were more pronounced in hypercholesterolemic rats (compared with control rats). Monoclonal antibodies against the adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 attenuated the I/R-induced leukocyte adherence and emigration and albumin leakage. Leukocyte adherence, but not albumin leakage, was diminished in animals pretreated with a P-selectin-specific antibody. Platelet aggregation was reduced by antibodies directed against either P-selectin, CD18, or intercellular adhesion molecule-1, as well as a GPIIb-IIIa antagonist. These results indicate that the enhanced reperfusion-induced albumin leakage in hypercholesterolemic rats is dependent on leukocyte-endothelial cell adhesion. Furthermore, P-selectin- and CD11/CD18-dependent heterotypic and GPIIb-IIIa-mediated homotypic platelet aggregation appear to influence the extravasation of both leukocytes and albumin in postischemic venules of hypercholesterolemic rats.

Neutrophil-dependent augmentation of PAF-induced vasoconstriction and albumin flux in coronary arterioles

1998 ◽  
Vol 275 (4) ◽  
pp. H1138-H1147 ◽  
Author(s):  
Qiaobing Huang ◽  
Mac Wu ◽  
Cynthia Meininger ◽  
Katherine Kelly ◽  
Yuan Yuan
Keyword(s):  
Platelet Activating Factor ◽  
Microvascular Dysfunction ◽  
Low Flow ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Apparent Permeability ◽  
Inflammatory Reactions ◽  
Coronary Arterioles ◽  
Flow Velocities

Platelet-activating factor (PAF) has been implicated in the pathogenesis of ischemic heart disease, reperfusion injury, and inflammatory reactions. Although neutrophils have been shown to primarily mediate PAF-induced microvascular dysfunction, the vasoactive effect of PAF and its neutrophil-dependent mechanism have not been directly and systematically studied in coronary resistance vessels. Therefore, the aim of this study was to examine the effects of PAF on coronary arteriolar function and neutrophil dynamics using an isolated and perfused microvessel preparation. Topical application of PAF to the vessels induced a dose-dependent decrease in the diameter but an increase in the apparent permeability coefficient of albumin. Disruption of the endothelium abolished the vasomotor response to PAF, and perfusion of neutrophils significantly augmented PAF-induced changes in vasomotor tone and permeability. Furthermore, the interaction between neutrophils and the endothelium was studied in the intact perfused coronary arterioles. Under control conditions, there were no adherent neutrophils observed in the vessels at varied intraluminal flow velocities. However, administration of PAF caused neutrophil adhesion to the endothelium of coronary arterioles at low flow velocities. Western blot analysis indicated that PAF upregulated the expression of intercellular adhesion molecule-1 in cultured coronary microvascular endothelial cells. Taken together, the results suggest that 1) PAF induces vasoconstriction and hyperpermeability in coronary arterioles via an endothelium-dependent and neutrophil-mediated mechanism, and 2) PAF is able to stimulate neutrophil adhesion in coronary arterioles under a condition of low flow rate.

ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy

1998 ◽  
Vol 274 (2) ◽  
pp. G246-G252 ◽  
Author(s):  
Z. Morise ◽  
S. Komatsu ◽  
J. W. Fuseler ◽  
D. N. Granger ◽  
M. Perry ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Critical Role ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Intercellular Adhesion Molecule ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
Mucosal Permeability

A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of 51Cr-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.

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