Protective actions of aspirin-triggered (17R) resolvin D1 and its analogue, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester, in C5a-dependent IgG immune complex-induced inflammation and lung injury.

Increasing evidence suggests that the novel anti-inflammatory and proresolving mediators such as the resolvins play an important role during inflammation. However, the functions of these lipid mediators in immune complex-induced lung injury remain unknown. In this study, we determined the role of aspirin-triggered resolvin D1 (AT-RvD1) and its metabolically stable analog, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester (p-RvD1), in IgG immune complex-induced inflammatory responses in myeloid cells and injury in the lung. We show that lung vascular permeability in the AT-RvD1- or p-RvD1-treated mice was significantly reduced when compared with values in mice receiving control vesicle during the injury. Furthermore, i.v. administration of either AT-RvD1 or p-RvD1 caused significant decreases in the bronchoalveolar lavage fluid contents of neutrophils, inflammatory cytokines, and chemokines. Of interest, AT-RvD1 or p-RvD1 significantly reduced bronchoalveolar lavage fluid complement C5a level. By EMSA, we demonstrate that IgG immune complex-induced activation of NF-kappa B and C/EBP beta transcription factors in the lung was significantly inhibited by AT-RvD1 and p-RvD1. Moreover, AT-RvD1 dramatically mitigates IgG immune complex-induced NF-kappa B and C/EBP activity in alveolar macrophages. Also, secretion of TNF-alpha, IL-6, keratinocyte cell-derived chemokine, and MIP-1 alpha from IgG immune complex-stimulated alveolar macrophages or neutrophils was significantly decreased by AT-RvD1. These results suggest a new approach to the blocking of immune complex-induced inflammation.