Complement-induced Vascular Leukostasis. Its Role in Tissue Injury

The plasma complement system evolved as a beneficial antimicrobial mechanism. However, this system can be activated chaotically in such situations as extracorporeal perfusion, trauma, sepsis, or acute pancreatitis. When so activated, the complement component C5a may aggregate granulocytes and cause leukoembolization; it is suggested that such leukoembolization is an important, previously unsuspected mechanism of tissue damage. In addition, toxic oxygen species, such as superoxide, that are produced by granulocytes that have been triggered by C5a can damage the endothelium, an event that may, if it occurs in the lungs, contribute to the development of the adult respiratory distress syndrome (ARDS). Hence the previously empiric use of high doses of corticosteroids in treating shock states, particularly in cases of the ARDS, may have a physiologic basis since very high concentrations of such drugs have been shown to inhibit both superoxide production and granulocyte aggregation.