The Role of Complement System in Septic Shock

Septic shock is a critical clinical condition with a high mortality rate. A better understanding of the underlying mechanisms is important to develop effective therapies. Basic and clinical studies suggest that activation of complements in the common cascade, for example, complement component 3 (C3) and C5, is involved in the development of septic shock. The involvement of three upstream complement pathways in septic shock is more complicated. Both the classical and alternative pathways appear to be activated in septic shock, but the alternative pathway may be activated earlier than the classical pathway. Activation of these two pathways is essential to clear endotoxin. Recent investigations have shed light on the role of lectin complement pathway in septic shock. Published reports suggest a protective role of mannose-binding lectin (MBL) against sepsis. Our preliminary study of MBL-associated serine protease-2 (MASP-2) in septic shock patients indicated that acute decrease of MASP-2 in the early phase of septic shock might correlate with in-hospital mortality. It is unknown whether excessive activation of these three upstream complement pathways may contribute to the detrimental effects in septic shock. This paper also discusses additional complement-related pathogenic mechanisms and intervention strategies for septic shock

MASP-2 activation is involved in ischemia-related necrotic myocardial injury in humans

BACKGROUND/OBJECTIVES: Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery. METHODS: A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA. RESULTS: MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I. CONCLUSIONS: These results indicate an involvement of MASP-2 in ischemia-related necrotic myocardial injury in humans