Targeted disruption of leukotriene B4 receptors BLT1 and BLT2: A critical role for BLT1 in collagen-induced arthritis in mice

Wen Hai Shao, Annalisa Del Prete, Cheryl B. Bock, Bodduluri Haribabu

Research output: Contribution to journalArticlepeer-review

Abstract

Leukotriene B4 mediates diverse inflammatory diseases through the G protein-coupled receptors BLT1 and BLT2. In this study, we developed mice deficient in BLT1 and BLT2 by simultaneous targeted disruption of these genes. The BLT1/BLT2 double-deficient mice developed normaly and peritoneal cxudate cells showed no detectable responses to leukqtriene B4 confirming the deletion of the BLT1/BLT2 locus. In a model of collagen-induced arthritis on the C57BL/6 background, the BLTt/BLT2-/- as well as the previously described BLT1-/- animals showed complete protection from disease development. The disease severity correlated well with histopathology, including loss of joint architecture, inflammatory cell infiltration, fibrosis, pannus formation, and bone erosion in joints of BLT1/BLT2+/+ animals and a total absence of disease pathology in leukotriene receptor-deficient mice. Despite these differences, all immunized BLT1-/- and BLT1/BLT2 -/- animals had similar serum levels of anti-collagen Abs relative to BLT1/BLT2+/+ animals. Thus, BLT1 may be a useful target for therapies directed at treating inflammation associated with arthritis.

Original languageEnglish
Pages (from-to)6254-6261
Number of pages8
JournalJournal of Immunology
Volume176
Issue number10
Publication statusPublished - May 15 2006

ASJC Scopus subject areas

  • Immunology

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