Inhibition of polymorphonuclear leukocytes by c3 split products in burned patients

Recent experimental and clinical evidence has pointed to the decreased ability of burn polymorphonuclear leukocyte (PMN) cells linked with serum-borne burn injury-related factors to develop phagocytosisconnected metabolic reaction (oxygen burst). In this study, burn patients’ PMNs showed an impaired rate of oxygen consumption during phagocytosis of opsonified zymosan, which correlated inversely with the degree of complement activation (measured as the ratio of C3d to native C3). Mimicking the burn condition (complement consumption), healthy donors’ PMN cells’ oxygen consumption rates were measured in the presence of normal and complement-activated normal serum (CoVF-, zymosan-, HAIgG-treated serum). Basal levels (resting state) of PMN oxygen consumption were higher, and oxygen uptake of stimulated cells was lower (dose dependence) in the presence of complement activation products. C3a or C3d removal (but not C3c) from burned or complement-activated normal serum resulted in an increase in burn and normal PMN oxygen consumption but not to normal levels. C3a and C3d protein fractions also inhibited PMN oxygen uptake upon stimulation. Results of this study suggest that PMNs subjected to complement activation products show a depressed ability to develop oxygen burst upon stimulation, which may contribute to neutrophil dysfunction in burns. Part of the observed alteration may be due to the presence of C3 split products. Possible mechanisms hypothesized to play a role in the development of C3 split products-related PMN alterations in burns are discussed on the basis of obtained results and data from relevant literature.