Quantitative measurement of P- and E-selectin adhesion molecules in acute pancreatitis. Correlation with distant organ injury

Andrew H. Lundberg, D. Neil Granger, Janice Russell, Omaima Sabek, James Henry, Lillian Gaber, Malak Kotb, A. Osama Gaber

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Objective. To determine whether expression of P- and E-selectin molecules is associated with the development of systemic organ manifestations in acute pancreatitis (AP). Summary Background Data. Overproduction of inflammatory cytokines in AP induces expression of adhesion molecules, which may lead to increased leukocytic infiltration and tissue damage. Understanding the temporal expression of these molecules could afford better measures for therapeutic intervention. Methods. Acute pancreatitis was induced in 30-day-old female C57/bl/6J mice by feeding a choline- deficient/ethionine-supplemented diet (n = 95). Mice were divided into three groups. Group I (n = 35) was used to study the biochemical and histologic manifestations of AP and to evaluate the neutrophilic infiltration by myeloperoxidase activity and immunofluorescence. Groups II (n = 35) and III (n = 25) were used to evaluate expression of P- and E-selectin by the dual radiolabeled monoclonal antibody technique. Results. Biochemical and histologic evidence of AP developed in all mice. The inflammatory cytokine tumor necrosis factor-α gradually increased in serum as early as 18 hours, reaching more than 800-fold background levels by 72 hours. Biphasic P- selectin expression in the lung was seen with peaks at 24 and 48 hours; E- selectin expression peaked at 48 hours. CD18-positive leukocytes and increased myeloperoxidase activity in the lung were demonstrated at 24 hours, correlating with the onset of selectin upregulation. Histologic scoring of lung tissue demonstrated mild damage at 24 hours, with progressive injury occurring from 48 to 72 hours. Conclusions. In AP, the production of inflammatory cytokines precedes upregulation of P- and E-selectin, whose expression coincided with the increased infiltration of CD18-positive cells and neutrophil sequestration in lung tissue. Temporally, these events correlate with evidence of histologic pulmonary injury and underscore the role of adhesion molecules as mediators of pathophysiologic events. This mechanistic pathway may afford novel therapeutic interventions in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.

Original languageEnglish (US)
Pages (from-to)213-222
Number of pages10
JournalAnnals of surgery
Volume231
Issue number2
DOIs
StatePublished - Feb 2000

ASJC Scopus subject areas

  • Surgery

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