マイクロパーティクル産生からみたｓｅｐｓｉｓの病態解明

Abstract

Leukocytes, platelets, and endothelial cells appear to co-activate and interact in areas of vascular injury following severe insult. Leukocyte adhesion to endothelium, a pivotal event in the host defense mechanism and repair of tissue damage, has been shown to induce vascular and tissue injury in sepsis. Microparticles (MPs) have been recently detected as vesicles that are shed from various kinds of activated cells, and they have specific membrane components. MPs originated from polymorphonuclear leukocytes (PMNLs), platelets, and endothelial cells were discovered in vitro by recently developed flow cytometric methods. PMNL-derived MPs have been recently found to be activators of vascular endothelium in vitro. Levels of platelet-derived MPs have been shown to be elevated in various conditions including unstable angina, diabetes, and post cardiac surgery. Endothelial cell-derived MPs are increased in patients with a coagulation abnormality characterized by the presence of lupus anticoagulant and in patients with acute coronary syndrome.These MPs are considered to activate other cells and to perhaps play a novel role in the pathogenesis of various diseases. The precise role of these MPs, however, has not been clarified in patients with sepsis. We developed a flow cytometric method for detecting these MP formation and quantitatively evaluating them in patients with sepsis. The production of each MP was significantly increased and the interaction between these MPs and other inflammatory cells was enhanced in the patients.This review will provide an overview of our current understanding of PMNL-, platelet- and endothelial cellderived MPs and their orchestration in sepsis patients.