| First Author | Chouchakova N | Year | 2001 |
| Journal | J Immunol | Volume | 166 |
| Issue | 8 | Pages | 5193-200 |
| PubMed ID | 11290803 | Mgi Jnum | J:123762 |
| Mgi Id | MGI:3719510 | Doi | 10.4049/jimmunol.166.8.5193 |
| Citation | Chouchakova N, et al. (2001) Fc gamma RIII-mediated production of TNF-alpha induces immune complex alveolitis independently of CXC chemokine generation. J Immunol 166(8):5193-200 |
| abstractText | We recently demonstrated a codominant role of C5aR and FcgammaRIII in the initiation of IgG immune complex-mediated inflammation in mice. In this study, we investigated the relative contribution of FcgammaRIII in the generation of several cytokines during experimental hypersensitivity pneumonitis/alveolitis in vivo. Induction of immune complex-alveolitis in C57BL/6 mice resulted in strong accumulation of neutrophils into the lung and enhanced chemotactic activity within bronchoalveolar lavage fluid accompanied by an increased production of the proinflammatory cytokines TNF-alpha and IL-1beta as well as the ELR-CXC chemokines macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC). FcgammaRIII-deficient C57BL/6 mice (FcgammaRIII(-/-)) showed a marked reduction of the inflammatory response due to decreased production of TNF-alpha, IL-1beta, and MIP-2. Results obtained in C57BL/6 mice either lacking the TNF-alpha class I receptor (TNF-alphaRI(-/-)) or treated with neutralizing anti-TNF-alpha mAb demonstrated an essential contribution of TNF-alpha for mediating IL-1beta release, neutrophil influx, and hemorrhage. Surprisingly, MIP-2 and KC chemokine levels remained largely unaffected in TNF-alphaRI(-/-) mice or after functional inhibition of TNF-alpha. These data suggest that in immune complex alveolitis, the activation of FcgammaRIII may induce divergent downstream effector pathways with TNF-alpha acting independently of CXC chemokines to trigger the inflammatory response in C57BL/6 mice. |
