Early expression changes of complement regulatory proteins (CRegs) and C5a receptor (CD88) on leukocytes after multiple injury in humans

摘要

As a crucial element of innate immunity, the complement cascade becomes activated after severe trauma. Regulation of the complement cascade and protection against complementmediated tissue destruction is provided by a selection of soluble and membrane-bound complement regulatory proteins (CRegs). To date, the leukocyte expression profile of CRegs in multiple injured patients is unknown. In the present study, expression of CRegs and the C5a receptor (CD88) was analyzed on neutrophils, monocytes and lymphocytes by flow cytometry. Whole blood samples were obtained from healthy volunteers (n=16) or multiple injured patients (n=12) on admission in the emergency room and 4, 12, 24, 120 and 240 hrs after trauma. The content of CRegs and CD88 on leukocytes was significantly altered post trauma: CD55 (decay accelerating factor) displayed a time dependent, elevated expression pattern on neutrophils and monocytes, but not on lymphocytes. CD59 (MAC inhibitor) expression was significantly increased on neutrophils and monocytes at the time of admission and after 5-10 d in lymphocytes. CD46 (membrane co-factor protein) was significantly down-regulated in all three cell types post trauma. CD35 (complement receptor 1) expression on neutrophils was initially decreased, while monocytes presented a significant increase in CD35 expression. CD35 on lymphocyte remained unchanged throughout the observation period. CD88 expression was considerably reduced on leukocytes between 0-240 hrs after injury. CD59, CD46 and CD88 expression values on neutrophils reversely correlated with severity of injury. In summary, expression profiles of CRegs and CD88 on leukocytes are specifically altered after polytrauma in humans, indicating a trauma-induced "complementopathy".