Distinct Tissue Site-Specific Requirements of Mast Cells and Complement Components C3/C5a Receptor in IgG Immune Complex-Induced Injury of Skin and Lung

摘要

We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at different tissue sites in mice lacking C3 treated or not with a CSaR-specific antagonist, or in mice lacking mast cells (Kit~W/Kit~(W-V) mice), and compared the inOammatory responses with those in the corresponding wild-type mice. We confirmed that IC inOammation of skin can be mediated largely by mast cells expressing CSaR and Fc#gamma#RIII. In addition, we provided evidence for C3-independent CSaR triggering, which may explain why the cutaneous Arthus reaction develops normally in C3~(-/-) mice. Furthermore, some, but not all, of the acute changes associated with the Arthus response in the lung were significantly more intense in normal mice than in C3~(-/-)or Kit~W/Kit~(W-V) mice, indicating for C3- and mast cell-dependent and -independent components. Finally, we demonstrated that C3 contributed to the elicitation of neutrophils to alveoli, which corresponded to an increased synthesis of TNF-#alpha#, macrophage-inOammatory protein-2, and cytokine. induced neutrophil chemoattractant. While mast cells similarly in8uenced alveolar polymorphonuclear leukocyte in8ux, the levels of these cytokines remained largely unaffected in mast cell deficiency. Together, the phenotypes of C3~(-/-)mice and Kit~W/Kit~(W-V) mice suggest that complement and mast cells have distinct tissue site-specific requirements acting by apparently distinct mech. anisms in the initiation of IC inOammation. The Journal of Immunology, 2001, 167: 1022-1027.