TY - JOUR
T1 - Targeted disruption of leukotriene B4 receptors BLT1 and BLT2
T2 - A critical role for BLT1 in collagen-induced arthritis in mice
AU - Shao, Wen Hai
AU - Del Prete, Annalisa
AU - Bock, Cheryl B.
AU - Haribabu, Bodduluri
PY - 2006/5/15
Y1 - 2006/5/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 16670336
AN - SCOPUS:33646484781
VL - 176
SP - 6254
EP - 6261
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -