Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN)

Objective ine 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. s al, 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. s RK6−/− 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. sions nd -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.