Verlust des neuen Decoy Rezeptors C5L2 während der experimentellen und klinischen Sepsis

Besides advanced surgical therapy and intensive care, sepsis often leads to fatal consequences and is therefore still a major problem of modern surgery. Both, extensive complement activation and associ-ated compromised cellular defence seem to play an important role in development and progression of sepsis. Recently, a second C5a receptor (C5L2) was detected on neutrophils and proposed to function as a »decoy receptor«. Therefore, present study was designed to determine the so far unknown role of C5L2 during experimental and clinical sepsis. Experimental sepsis was induced by cecal ligation and puncture (CLP) of Long-Evans rats (250–300 g). After induction of sepsis, some rats received 400 ug of either anti-C5a IgG or preimmune IgG intravenously. After given time periods, animals were sacrificed, neutrophils isolated and C5L2 content investigated. Furthermore, neutrophils obtained from patients with severe sepsis or septic shock were analyzed by flowcytometry or immu-noblot for their C5L2 expression (with the permission of the Independent Local Ethics Committee of the University of Ulm, approval No. 82/2002). Following CLP in rats, neutrophils demonstrated a time-dependent decrease in C5L2. In vivo blockade of C5a during experimental sepsis resulted in preservation of C5L2, which was associated with a significant improvement of survival. Similarly, neutrophils from patients with progressive sepsis showed significantly reduced C5L2 expression (n = 26) which was virtually abolished in patients who developed multi-organ failure (n = 10). In contrast, sepsis survivors exhibited retention of C5L2 (n = 12/13). The data suggest that C5L2 on neutrophils diminishes during sepsis. Blockade of excessive C5a externally by anti-C5a IgG or inter-nally by C5L2 might attenuate development of sepsis and improve survival during sepsis.