Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion

Davenpeck, Kelly L.; Gauthier, Theresa W.; Albertine, Kurt H.; Lefer, Allan M.

doi:10.1152/ajpheart.1994.267.2.h622

Cited by 47 publications

(38 citation statements)

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“…Similar results have been obtained in rats subjected to ischemia-reperfusion of the mesentery. These rats were administered the same anti-Pselectin antibody intravenously as that used in the present study (29). In this regard, L-NAME has been effectively used to up-regulate leukocyte-endothelium interaction, because the increased adherence mediated by L-NAME is not due to direct leukocyte activation (19).…”

Section: Discussionmentioning

confidence: 99%

Lipoxin A₄stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Scalia

Gefen

Petasis

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

105

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Three different stable lipoxin A 4 (LXA 4 ) analogs (i.e., 16-phenoxy-LXA 4 -Me, 15-cyclohexyl-LXA 4 -Me, and 15-R/S-methyl-LXA 4 -Me) were studied for their ability to modulate leukocyte-endothelial cell interactions in the rat mesenteric microvasculature. Superfusion of the rat mesentery with 50 mol/liter N G-nitro-L-arginine methyl ester (L-NAME) caused a significant, time-dependent increase in leukocyte rolling (56 ؎ 8 cells/min; P < 0.01 vs. control) and leukocyte adherence (12.5 ؎ 1.2 cells/100 m length of venule; P < 0.01 vs. control) after 120 min of superfusion. Concomitant superfusion of the rat mesentery with 10 nmol/liter of each of three lipoxin analogs consistently and markedly attenuated L-NAME-induced leukocyte rolling to 10 ؎ 4 (P < 0.01), 4 ؎ 1 (P < 0.01), and 32 ؎ 7 (P < 0.05) cells/min, and adherence to 4 ؎ 0.8 (P < 0.01), 1.1 ؎ 0.4 (P < 0.01), and 7 ؎ 0.7 (P < 0.05) cells/100 m length of venule (16-phenoxy-LXA 4 -Me, 15-cyclohexyl-LXA 4 -Me, and 15-R/S-methyl-LXA 4 -Me, respectively). No alterations of systemic blood pressure or mesenteric venular shear rates were observed in any group. Immunohistochemical up-regulation of P-selectin expression on intestinal venular endothelium was significantly increased (P < 0.01) after exposure to L-NAME, and this was significantly attenuated by these lipoxin analogs (P < 0.01). Thus, in vivo superfusion of the rat mesentery with stable lipoxin analogs at 10 nmol/liter reduces L-NAME-induced leukocyte rolling and adherence in the mesenteric rat microvasculature by attenuating P-selectin expression. This anti-inf lammatory mechanism may represent a novel and potent regulatory action of lipoxins on the immune system.Lipoxins represent a relatively new class of arachidonic acid derivatives (i.e., trihydroxytetraene eicosanoids) that are produced by activated leukocytes, which, in turn, are able to modulate leukocyte functions (1). In vitro data indicate that one member of the naturally occurring lipoxins, (i.e., lipoxin A 4 , namely LXA 4 ), inhibits both neutrophil and eosinophil chemotaxis at nanomolar concentrations (2, 3) and blocks polymorphonuclear neutrophil (PMN) transmigration across epithelial cells (4) and endothelial monolayers (5). Similar actions also are demonstrable in vivo where LXA 4 exerts vasodilator properties (6-9), blocks both PMN diapedesis from postcapillary venules (10), and inhibits PMN entry in inflamed renal tissues in animal models of glomerulonephritis (11).Nevertheless, we know of no specific information elucidating detailed mechanisms by which naturally occurring lipoxins and their synthetic stable analogs can directly modulate the interaction of leukocytes with vascular endothelial cells. LXA 4 , as with other autacoids, is rapidly inactivated in the local extracellular milieu. Analogs of LXA 4 were designed and prepared by total organic synthesis so that they resist rapid inactivation and retain potent biological activities (12). A goal of this study was to use these metabolically stable analogs to investigate the i...

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Section: Discussionmentioning

confidence: 99%

Lipoxin A₄stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Scalia

Gefen

Petasis

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

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“…Endothelial cell surface expression of P-selectin (CD62), an integral membrane protein rapidly translocated to the plasma membrane during exocytosis of the Weibel-Palade bodies, promotes the binding and "rolling" of neutrophils, which precedes their migration into sites of inflammation (35)(36)(37)(38)(39)(40)(41). To investigate the mechanism responsible for the reduced PMN infiltration in GC-A-deficient mice, we examined P-selectin expression after ischemia/reperfusion.…”

Section: Decreased Myocardial Infarct Size In Gc-a -/-Mice the Heartmentioning

confidence: 99%

Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-κB activation and alleviates myocardial ischemia/reperfusion injury

Izumi

Saito

Kishimoto³

et al. 2001

J. Clin. Invest.

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Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H 2 O 2 -induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-κB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-κB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury. uretic peptide signaling on the size of myocardial infarcts evoked by protocols of ischemia and reperfusion. Methods Animals. GC-A-deficient (GC-A -/-) mice and their GC-A +/+littermates (wild-type controls) were generated as described previously (26). All mice used in this study were between 10 and 14 weeks old. C57BL/6 (10-14 weeks) mice were purchased from Shimizu Co. (Kyoto, Japan). All experimental procedures were performed according to Kyoto University standards for animal care.Surgical procedures. Mice were initially anesthetized with ether and placed on a warm pad maintained at 37°C. The trachea of each mouse was cannulated with a polyethylene tube connected to a respirator (Shinano Co., Tokyo, Japan) with a tidal volume set at 0.6 ml and a rate set at 110/min. The mice were then anesthetized with 0.5-1.5% isoflurane for the remainder of the surgical procedure. After a 10-minute equilibration period, a left thoracotomy was performed between the fourth and fifth ribs. The pericardial sac was then removed, and the left anterior descending artery (LAD) was visualized under a microscope and ligated with a 7-0 silk suture using a snare occluder. To avoid injuring the LAD, a small patch was attached to its surface. Ischemia and reperfusion were accomplished by first tightening the snare occluder and then loosening it. Significant electrocardiogram and color changes at the area at risk (AAR) were considered indicative of successful coronary occlusion and reperfusion. The silk suture was left in place, and chests of the mice were closed with 5-0 silk sutures. The animals were then weaned from the respirator, and the intratracheal tube was removed once they were breathing spontaneously and began to move.Myo...

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“…This rolling process is a prerequisite for firm adherence in these vessels and the subsequent transendothelial migration of neutrophils [12,13]. In other words, anti-P-selectin antibodies that reduce rolling, will also reduce the number of adherent neutrophils and therefore reduce the extent of neutrophilinduced injury in organs such as the heart [18,19], intestine [22], and lung [20,21]. In contrast to these findings, our data clearly demonstrated that a blocking anti-P-selectin antibody neither reduced the number of accumulating neutrophils in sinusoids at any time nor attenuated liver injury.…”

Section: Figmentioning

confidence: 99%

Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock

Essani¹,

Fisher²,

Simmons³

et al. 1998

Journal of Leukocyte Biology

132

158

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We studied the role of P-selectin, an adhesion molecule known to be important for neutrophil localization to sites of inflammation, in a model of inflammatory liver injury. Male C3Heb/ FeJ (ET-sensitive) mice treated with 700 mg/kg galactosamine and 100 g/kg Salmonella abortus equi endotoxin (Gal/ET), murine tumor necrosis factor ␣ (TNF-␣, 15 g/kg), or interleukin-1 (IL-1, 13-23 g/kg), showed increased P-selectin mRNA levels in the liver. In contrast, C3H/HeJ (ET-resistant) mice responded only to cytokines with P-selectin mRNA formation. Whereas no P-selectin expression was detectable in control livers, there was temporary staining of endothelium in large blood vessels but not in sinusoids between 3 and 5 h after ET, TNF-␣, or IL-1 treatment. Severe liver injury induced by Gal/ET at 7 h was not inhibited by an anti-P-selectin antibody in C3Heb/FeJ mice or in P-selectin-deficient animals. Sequestration of neutrophils in sinusoids, i.e. those neutrophils that have been identified as critical for the injury, was not affected by the antibody or in P-selectindeficient mice. However, the temporary margination in portal and post-sinusoidal venules was reduced by 75% in anti-P-selectin antibody-treated animals and by 51% in P-selectin-deficient mice. We conclude that hepatic P-selectin gene transcription in vivo involves cytokines. However, blocking P-selectin neither attenuated sinusoidal neutrophil sequestration nor prevented neutrophil-induced liver injury during endotoxin shock but attenuated neutrophil margination in larger vessels. Thus, our data demonstrate similarities and fundamental differences in the requirement for adhesion molecules to localize neutrophils in the liver vasculature compared to other organs during an inflammatory response.

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Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion

Cited by 47 publications

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Lipoxin A₄stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Lipoxin A₄stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-κB activation and alleviates myocardial ischemia/reperfusion injury

Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock

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Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion

Cited by 47 publications

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Lipoxin A4stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Lipoxin A4stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-κB activation and alleviates myocardial ischemia/reperfusion injury

Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock

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Lipoxin A₄stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

Lipoxin A₄stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin