| First Author | Tarrant TK | Year | 2008 |
| Journal | Clin Immunol | Volume | 129 |
| Issue | 1 | Pages | 115-22 |
| PubMed ID | 18662895 | Mgi Jnum | J:140405 |
| Mgi Id | MGI:3813749 | Doi | 10.1016/j.clim.2008.06.008 |
| Citation | Tarrant TK, et al. (2008) Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol 129(1):115-22 |
| abstractText | OBJECTIVE: Chemokine receptors are G-protein coupled receptors (GPCRs) phosphorylated by G-protein receptor kinases (GRKs) after ligand-mediated activation. We hypothesized that GRK subtypes differentially regulate granulocyte chemotaxis and clinical disease expression in the K/BxN model. METHODS: Clinical, histologic, and cytokine responses in GRK6-/-, GRK5-/-, GRK2+/-, and wildtype mice were evaluated using K/BxN serum transfer. Granulocyte chemotaxis was analyzed by transendothelial migration assays. RESULTS: Both GRK6-/- and GRK2+/- mice had increased arthritis disease severity (p<0.001); whereas GRK5-/- was not different from controls. Acute weight loss was enhanced in GRK6-/- and GRK2+/- mice (p<0.001, days 3-10). However, GRK6-/- mice uniquely had more weight loss (>10%), elevated serum IL-6, and enhanced migration toward LTB4 and C5a in vitro. CONCLUSIONS: GRK6 and -2, but not GRK5, are involved in the pathogenesis of acute arthritis in the K/BxN model. In particular, GRK6 may dampen inflammatory responses by regulating granulocyte trafficking toward chemoattractants. |
