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 this investigation was to evaluate the influence of ROI generation on neutrophil adhesion molecule regulation and degranulation. Induction of the neutrophil oxidative burst via Fcgamma receptor cross-linking was accompanied by up-regulation of neutrophil surface CD11b, CD35, and CD66b only in the presence of selected serum proteins, such as purified human C4, C5, or human serum albumin (HSA). Scavenging of ROI attenuated protein-dependent receptor regulations. Moreover, exogenous hydrogen peroxide was effective to increase neutrophil CD11b expression in a protein-dependent way. HSA exposed to neutrophil-derived ROI displayed signs of oxidative modification in terms of carbonyl formation. Such modified HSA transferred to resting neutrophils bound readily to the cell surface and effected receptor modulation as well as cellular spreading. In contrast, neither native HSA nor HSA protected against 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 neutrophil stimulation.
Körmöczi
G F
GF
Institute of Immunology, University of Vienna, Vienna, Austria. guenther.koermoeczi@univie.ac.at
Wölfel
U M
UM
Rosenkranz
A R
AR
Hörl
W H
WH
Oberbauer
R
R
Zlabinger
G J
GJ
D001798:Blood Proteins / Q000378:metabolism* / Q000502:physiology; D003181:Complement C4 / Q000502:physiology; D003182:Complement C5 / Q000502:physiology; D015936:Complement C5a / Q000502:physiology; D010450:Endopeptidases / Q000097:blood / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000502:physiology; D007399:Interphase / Q000502:physiology; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D016877:Oxidants / Q000097:blood / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface / Q000097:blood; D016897:Respiratory Burst / Q000502:physiology; D012709:Serum Albumin / Q000378:metabolism / Q000502:physiology
D001798:Blood Proteins; D003181:Complement C4; D003182:Complement C5; D016166:Free Radical Scavengers; D007074:Immunoglobulin G; D016877:Oxidants; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D015936:Complement C5a; D006861:Hydrogen Peroxide; D010450:Endopeptidases