Serum proteins modified by neutrophil-derived oxidants as mediators of neutrophil stimulation

Reactive oxygen intermediates (ROI) released during inflammation may act as important mediators of neutrophil effector functions. The objective of thi s investigation was to evaluate the influence of ROI generation on neutroph il adhesion molecule regulation and degranulation. Induction of the neutrop hil oxidative burst via Fc gamma receptor cross-linking was accompanied by upregulation of neutrophil surface CD11b, CD35, and CD66b only in the prese nce of selected serum proteins, such as purified human C4, C5, or human ser um albumin (HSA). Scavenging of ROI attenuated protein-dependent receptor r egulations. Moreover, exogenous hydrogen peroxide was effective to increase neutrophil CD11b expression in a protein-dependent way. HSA exposed to neu trophil-derived ROI displayed signs of oxidative modification in terms of c arbonyl formation. Such modified HSA transferred to resting neutrophils bou nd readily to the cell surface and effected receptor modulation as well as cellular spreading. In contrast, neither native HSA nor HSA protected again st oxidation by the tocopherol analog Trolox exhibited agonistic properties . In conclusion, we demonstrate that neutrophil-derived ROI modify selected serum proteins, which, in turn, act as proinflammatory mediators of neutro phil stimulation. The Journal of Immunology, 2001.