| First Author | Wiege K | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 1 | Pages | 324-33 |
| PubMed ID | 23225882 | Mgi Jnum | J:190819 |
| Mgi Id | MGI:5449761 | Doi | 10.4049/jimmunol.1201398 |
| Citation | Wiege K, et al. (2013) Galphai2 is the essential galphai protein in immune complex-induced lung disease. J Immunol 190(1):324-33 |
| abstractText | Heterotrimeric G proteins of the Galpha(i) family have been implicated in signaling pathways regulating cell migration in immune diseases. The Galpha(i)-protein-coupled C5a receptor is a critical regulator of IgG FcR function in experimental models of immune complex (IC)-induced inflammation. By using mice deficient for Galpha(i2) or Galpha(i3), we show that Galpha(i2) is necessary for neutrophil influx in skin and lung Arthus reactions and agonist-induced neutrophilia in the peritoneum, whereas Galpha(i3) plays a less critical but variable role. Detailed analyses of the pulmonary IC-induced inflammatory response revealed several shared functions of Galpha(i2) and Galpha(i3), including mediating C5a anaphylatoxin receptor-induced activation of macrophages, involvement in alveolar production of chemokines, transition of neutrophils from bone marrow into blood, and modulation of CD11b and CD62L expression that account for neutrophil adhesion to endothelial cells. Interestingly, C5a-stimulated endothelial polymorphonuclear neutrophil transmigration, but not chemotaxis, is enhanced versus reduced in the absence of neutrophil Galpha(i3) or Galpha(i2), respectively, and knockdown of endothelial Galpha(i2) caused decreased transmigration of wild-type neutrophils. These data demonstrate that Galpha(i2) and Galpha(i3) contribute to inflammation by redundant, overlapping, and Galpha(i)-isoform-specific mechanisms, with Galpha(i2) exhibiting unique functions in both neutrophils and endothelial cells that appear essential for polymorphonuclear neutrophil recruitment in IC disease. |
