Elevation of rat plasma P-selectin in acute lung injury

Abstract

Acute lung injury in the rat caused by intravenous (i.v.) infusion of cobra venom factor (CVF) or lipopolysaccharide (LPS) is mediated by P-selectin-dependent neutrophil infiltration into the lung. In these lung injury models, P-selectin expression is induced on lung vascular endothelial cells after the CVF or LPS infusion, suggesting soluble P-selectin derived from inflamed sites might also be elevated. Here we established a sensitive enzyme-linked immunosorbent assay (ELISA) to measure soluble P-selectin in plasma, a potential marker of lung injury. Nine anti-rat P-selectin monoclonal antibodies that we established previously were first classified into 5 groups based on real-time biospecific interaction analyses, and used to develop a sandwich ELISA for accurately measuring the amount of soluble P-selectin in plasma. We then used this ELISA to measure the plasma P-selectin levels in Long Evans, Wistar, and Sprague-Dawley rats after the i.v. infusion of CVF or LPS. The elevation in P-selectin levels was significantly different among the strains, but it consistently correlated with the extent of lung inflammation, measured by myeloperoxidase levels in the lung tissues. Thus, our results indicate that the soluble P-selectin in plasma could serve as a sensitive biomarker reflecting lung inflammation, which is of clinical importance for detecting and preventing severe lung injury.

Circulating adhesion molecules and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

“…Little is known about the role of P-selectin in the development of fibrosis, but there are substantial data supporting the role of platelets and P-selectin in acute lung injury, which is particularly relevant given that repetitive injury to alveolar membrane has been implicated in the development of ILD, and subclinical ILD has been linked to increased risk of acute respiratory distress syndrome [33]. In animal models of acute lung injury, plasma levels of P-selectin correlated with the extent of lung inflammation after infusion of lipopolysaccharide, and an increase in platelet-derived P-selectin led to downstream ICAM-1 expression and neutrophil activation [34,35]. In patients with acute respiratory distress syndrome, plasma P-selectin levels are associated with both higher lung injury scores and increased mortality [2,15].…”

Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation

“…Endotoxin-induced lung injury is characterized by migration of neutrophils into lung tissues, and migration of activated neutrophils, although necessary for host defense, is credited with excessive tissue damage. There are studies demonstrating the role of selectins and integrins (15,69), along with various chemokines, in recruitment of neutrophils into low microvascular pressure environment of the lungs (1, 50 -52, 66). Our data are the first to show that LSP1 deficiency reduces lung pathology and migration of neutrophils into alveoli and interstitium of inflamed lungs.…”

Contribution of Neutrophils to Acute Lung Injury

“…In contrast, all selectins are involved in the progress of lung injury caused by activation of complement or intratracheal application of IgG (40,41). Moreover, severity of ALI in the rat caused by infusion of cobra venom factor (VCF) or LPS correlates with P-selectin plasma levels (42). Experimental data suggest that inhibition or deletion of one or more selectins protects from ALI (43)(44)(45).…”