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

Objective To determine whether expression of P- and E-selectin molecules is associate d with the development of systemic organ manifestations in acute pancreatit is (AP). Summary Background Data Overproduction of inflammatory cytokines in AP induces expression of adhesi on molecules, which may lead to increased leukocytic infiltration and tissu e damage. Understanding the temporal expression of these molecules could af ford better measures for therapeutic intervention. Methods Acute pancreatitis was induced in 30-day-old female C57/ bI/6J mice by feed ing a choline-deficient/ethionine-supplemented diet (n = 95), Mice were div ided into three groups. Group I (n = 35) was used to study the biochemical and histologic manifestations of AP and to evaluate the neutrophilic infilt ration by myeloperoxidase activity and immunofluorescence, Groups II (n = 3 5) and iii (n = 25) were used to evaluate expression of P- and E-selectin b y the dual radiolabeled monoclonal antibody technique. Results Biochemical and histologic evidence of AP developed in all mice. The inflam matory cytokine tumor necrosis factor-alpha gradually increased in serum as early as 18 hours, reaching more than 800-fold background levels by 72 hou rs. Biphasic P-selectin expression in the lung was seen with peaks at 24 an d 48 hours; E-selectin expression peaked at 48 hours, CD18-positive leukocy tes 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 progressi ve 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, Tempor ally, these events correlate with evidence of histologic pulmonary injury a nd underscore the role of adhesion molecules as mediators of pathophysiolog ic events, This mechanistic pathway may afford novel therapeutic interventi ons in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.