Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung

J Immunol. 2001 Jul 15;167(2):1022-7. doi: 10.4049/jimmunol.167.2.1022.


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 C5aR-specific antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the inflammatory responses with those in the corresponding wild-type mice. We confirmed that IC inflammation of skin can be mediated largely by mast cells expressing C5aR and FcgammaRIII. In addition, we provided evidence for C3-independent C5aR 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-inflammatory protein-2, and cytokine-induced neutrophil chemoattractant. While mast cells similarly influenced alveolar polymorphonuclear leukocyte influx, 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 mechanisms in the initiation of IC inflammation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Arthus Reaction / immunology
  • Arthus Reaction / metabolism
  • Arthus Reaction / pathology
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Complement C3 / deficiency
  • Complement C3 / genetics
  • Complement C3 / physiology*
  • Complement C5a / physiology*
  • Cytokines / biosynthesis
  • Immune Complex Diseases / immunology*
  • Immune Complex Diseases / metabolism
  • Immune Complex Diseases / pathology
  • Immunoglobulin G / physiology*
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mast Cells / immunology*
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement / physiology*
  • Skin / immunology*
  • Skin / metabolism
  • Skin / pathology


  • Antigens, CD
  • Complement C3
  • Cytokines
  • Immunoglobulin G
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Complement C5a