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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tarrant, TK; Rampersad, RR; Esserman, D; Rothlein, LR; Liu, P; Premont, RT; Lefkowitz, RJ; Lee, DM; Patel, DD

Published Date

  • October 2008

Published In

Volume / Issue

  • 129 / 1

Start / End Page

  • 115 - 122

PubMed ID

  • 18662895

Pubmed Central ID

  • 18662895

Electronic International Standard Serial Number (EISSN)

  • 1521-7035

Digital Object Identifier (DOI)

  • 10.1016/j.clim.2008.06.008

Language

  • eng

Conference Location

  • United States