Neutrophil elicitation in the reverse passive Arthus reaction. Complement-dependent and -independent mast cell involvement.
Previous investigations in our laboratory have shown that mast cells play a significant role in the initiation of immune complex-mediated inflammation. Histamine, leukotrienes, and TNF released from mast cells are important mediators of early inflammatory processes. In the peritoneal reverse passive Arthus reaction, we observed a biphasic release of TNF. Mast cells were responsible for the first peak. The complement system is also known to be central to the expression of antibody-induced immune injury. Therefore, in this study, we investigated the significance of activated complement in regulating mast cell stimulation and neutrophil recruitment in the peritoneal reverse passive Arthus reaction. Mast cell degranulation and the release of TNF during the initiation of inflammation were blocked by decomplementation and C5 deficiency. Mast cell degranulation later in the reaction was complement-independent. Therefore, mast cells were activated in vivo in antibody-mediated injury by two different mechanisms, early in the reaction by complement and later by an unknown stimulus. Both mast cells and intact complement were also required for the full expression of neutrophil influx and release of TNF in the later phase. In fact, activated complement and mast cell mediators seemed to be the only factors necessary for the initiation of neutrophil recruitment. The findings significantly contribute to the understanding of the mechanisms involved in the induction of inflammatory processes in immune complex-mediated injury.
Ramos
B F
BF
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
Zhang
Y
Y
Jakschik
B A
BA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001183:Arthus Reaction / Q000276:immunology*; D015550:Cell Degranulation; D003182:Complement C5 / Q000172:deficiency; D003165:Complement System Proteins / Q000502:physiology*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000936:Antigen-Antibody Complex; D003182:Complement C5; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins