Disease relevance of Ltb4r2

• 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 [1].
• Chinese hamster ovary cells expressing BLT2 exhibit LTB(4)-induced chemotaxis, calcium mobilization, and pertussis toxin-insensitive inhibition of adenylyl cyclase [2].

High impact information on Ltb4r2

• BLT2 is expressed ubiquitously, in contrast to BLT1, which is expressed predominantly in leukocytes [2].
• Several BLT1 antagonists, including U 75302, failed to inhibit LTB(4) binding to BLT2 [2].
• BLT2 is highly homologous to BLT1, with an amino acid identity of 45.2%, and its open reading frame is located in the promoter region of the BLT1 gene [2].
• Leukotriene B(4) mediates diverse inflammatory diseases through the G protein-coupled receptors BLT1 and BLT2 [1].
• These data suggest the presence of functional BLT2 in primary keratinocytes [3].

Biological context of Ltb4r2

• Characterization of a mouse second leukotriene B4 receptor, mBLT2: BLT2-dependent ERK activation and cell migration of primary mouse keratinocytes [3].
• BLT1 and BLT2 are high- and low-affinity LTB4 receptors, respectively, and form a gene cluster in human and mouse [4].

Anatomical context of Ltb4r2

• Northern blot analysis showed that mouse BLT2 is expressed highly in small intestine and skin in contrast to the ubiquitous expression of human BLT2 [3].
• Thus, BLT2 is a pharmacologically distinct receptor for LTB(4), and may mediate cellular functions in tissues other than leukocytes [2].

Analytical, diagnostic and therapeutic context of Ltb4r2

• By in situ hybridization and the reverse transcriptase polymerase chain reaction, we demonstrated that mouse BLT2 is expressed in follicular and interfollicular keratinocytes [3].
• In a model of collagen-induced arthritis on the C57BL/6 background, the BLT1/BLT2(-/-) as well as the previously described BLT1(-/-) animals showed complete protection from disease development [1].
• Here, we report the molecular cloning of a novel GPCR for LTB(4), designated BLT2, which binds LTB(4) with a Kd value of 23 nM compared with 1.1 nM for BLT1, but still efficiently transduces intracellular signaling [2].

References