CHANGES IN LYMPHOCYTE ADHESION MOLECULE EXPRESSION IN ACUTE PANCREATITIS.

Abstract

Background and Aim: Pancreatitis induces many changes in inflammatory cells, but its effect on cell surface expression profiles of lymphocyte adhesion molecules in different tissues of the same subject remains unclear. In this study, we investigated changes in cell surface expression profiles of helper/cytotoxic T cells (CD4, CD8), T cell receptors (TCR)(αβ, γδ), and adhesion molecules including selectin (CD62L) and integrins (CD11a, CD49d) on lymphocytes derived from either whole blood or spleen obtained from pancreatitis induced rats, compared with healthy controls. Methods: Acute pancreatitis (AP) was induced in Wistar rats by retrograde infusion of 4% sodium taurocholate into the pancreatic duct. Whole blood and spleen from AP and healthy rats were harvested at 24 hr. Peripheral blood mononuclear cells (PBMC) were separated from each organ (Ficoll-Paque) and incubated with conjugated antibodies. Expression of cell surface antigens was determined by flow cytometry. Results:Splenic-derived lymphocytes (SDL): There was minimal expression of CD4+ and CD8+ T lymphocytes derived from AP rats (<2% and 3% respectively), compared with healthy controls (34% and 28% respectively). TCR expression was predominantly αβ in AP and healthy rats (66% and 58%, respectively) (<1% γ δ in both groups). Adhesion molecule expression of CD62L+ cells showed a 9-fold reduction in AP compared with controls (6% and 56%, respectively) and expression CD11a+ was also reduced (52% and 73%, respectively). Minimal expression of CD49d was observed in both groups (2% and 3%, respectively). Blood-derived lymphocytes (BDL): There was minimal expression of CD4+T lymphocytes derived from AP rats, compared with controls (<2% and 35%, respectively). Similar expression was observed for CD8+ T cells in both groups (12% and 16%, respectively). The T cell CD4/CD8 ratio was reversed in AP compared with controls. TCR expression was predominantly αβ in AP and normal rats (66% and 50%, respectively) (<1% γ δ in both groups). Adhesion molecule expression of CD62L+ cell showed a 2-fold reduction in AP lymphocytes compared with controls (33% and 76%, respectively) and expression of CD11a+ cells was similar in both groups (40% and 42%, respectively); expression of CD49d+ cells showed a >4-fold decrease in AP lymphocytes compared with healthy controls (4% and 18%, respectively). Conclusions: Pancreatitis induces appreciable changes in both SDL and BDL T cell and adhesion molecule expression and minimal changes in TCR. These changes may elucidate migration patterns of lymphocytes and lead to novel approaches for immunotherapy in acute pancreatitis.