| First Author | Wiege K | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 2 | Pages | 980-7 |
| PubMed ID | 22706085 | Mgi Jnum | J:189540 |
| Mgi Id | MGI:5446089 | Doi | 10.4049/jimmunol.1200891 |
| Citation | Wiege K, et al. (2012) Defective macrophage migration in Galphai2- but not Galphai3-deficient mice. J Immunol 189(2):980-7 |
| abstractText | Various heterotrimeric G(i) proteins are considered to be involved in cell migration and effector function of immune cells. The underlying mechanisms, how they control the activation of myeloid effector cells, are not well understood. To elucidate isoform-redundant and -specific roles for Galpha(i) proteins in these processes, we analyzed mice genetically deficient in Galpha(i2) or Galpha(i3). First, we show an altered distribution of tissue macrophages and blood monocytes in the absence of Galpha(i2) but not Galpha(i3). Galpha(i2)-deficient but not wild-type or Galpha(i3)-deficient mice exhibited reduced recruitment of macrophages in experimental models of thioglycollate-induced peritonitis and LPS-triggered lung injury. In contrast, genetic ablation of Galpha(i2) had no effect on Galpha(i)-dependent peritoneal cytokine production in vitro and the phagocytosis-promoting function of the Galpha(i)-coupled C5a anaphylatoxin receptor by liver macrophages in vivo. Interestingly, actin rearrangement and CCL2- and C5a anaphylatoxin receptor-induced chemotaxis but not macrophage CCR2 and C5a anaphylatoxin receptor expression were reduced in the specific absence of Galpha(i2). Furthermore, knockdown of Galpha(i2) caused decreased cell migration and motility of RAW 264.7 cells, which was rescued by transfection of Galpha(i2) but not Galpha(i3). These results indicate that Galpha(i2), albeit redundant to Galpha(i3) in some macrophage activation processes, clearly exhibits a Galpha(i) isoform-specific role in the regulation of macrophage migration. |
