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

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

Publication , Journal Article

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

Published in: Clin Immunol

October 2008

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.

Duke Scholars

Author Robert J. Lefkowitz Medicine, Cardiology

Author Teresa Kathleen Tarrant Medicine, Rheumatology and Immunology

Published In

Clin Immunol

DOI

10.1016/j.clim.2008.06.008

EISSN

1521-7035

Publication Date

October 2008

Volume

129

Issue

Start / End Page

115 / 122

Location

United States

Related Subject Headings

Mice, Knockout
Mice, Inbred C57BL
Mice
Male
Leukotriene B4
Interleukin-6
Immunology
Granulocytes
G-Protein-Coupled Receptor Kinases
G-Protein-Coupled Receptor Kinase 2

Citation

APA

Chicago

ICMJE

MLA

NLM

Tarrant, T. K., Rampersad, R. R., Esserman, D., Rothlein, L. R., Liu, P., Premont, R. T., … Patel, D. D. (2008). Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol, 129(1), 115–122. https://doi.org/10.1016/j.clim.2008.06.008

Tarrant, Teresa K., Rishi R. Rampersad, Denise Esserman, Lisa R. Rothlein, Peng Liu, Richard T. Premont, Robert J. Lefkowitz, David M. Lee, and Dhavalkumar D. Patel. “Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN).” Clin Immunol 129, no. 1 (October 2008): 115–22. https://doi.org/10.1016/j.clim.2008.06.008.

Tarrant TK, Rampersad RR, Esserman D, Rothlein LR, Liu P, Premont RT, et al. Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol. 2008 Oct;129(1):115–22.

Tarrant, Teresa K., et al. “Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN).” Clin Immunol, vol. 129, no. 1, Oct. 2008, pp. 115–22. Pubmed, doi:10.1016/j.clim.2008.06.008.

Tarrant TK, Rampersad RR, Esserman D, Rothlein LR, Liu P, Premont RT, Lefkowitz RJ, Lee DM, Patel DD. Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol. 2008 Oct;129(1):115–122.