Activated Platelets in Ulcerative Colitis Enhance the Production of Reactive Oxygen Species by Polymorphonuclear Leukocytes

Abstract

Background: Although the number of activated platelets increases in the peripheral blood of patients with inflammatory bowel disease (IBD), the role of activated platelets in the polymorphonuclear leukocytes (PMN)-mediated mucosal injury in IBD remains unclear. In the present study, we used luminol-enhanced chemiluminescence (LCL) to examine the influence of platelets from patients with ulcerative colitis (UC) on the production of reactive oxygen species (ROS) by circulating PMN. Methods: The proportion of P-selectin-positive activated platelets was determined using flow cytometry. PMN from patients with UC and normal controls were stimulated using phorbol 12-myristate 13-acetate with or without autologous platelets, anti-P-selectin monoclonal antibody and thrombin. Indicator PMN from a normal volunteer were stimulated using heterologous platelets from UC patients and normal controls, and LCL signals were registered every 60 sec for 240 min. Results: The proportion of activated platelets was significantly increased in IBD patients. The level of ROS production by PMN did not significantly differ between UC patients and normal controls in the absence of a platelet-PMN interaction. Platelets from UC patients enhanced the amount of ROS produced by indicator PMN significantly more than those from normal controls. This effect was partly diminished by anti-P-selectin monoclonal antibody. Conclusions: Platelet activation in UC might be responsible for the secondary activation of PMN, which could account for the increase in PMN-mediated tissue injury associated with UC.

• Chemiluminescence Platelet Activation Polymorphonuclear Leukocytes P-SELECTIN Reactive Oxygen Species Ulcerative Colitis