出版社：American Society for Biochemistry and Molecular Biology
摘要：Lysophosphatidic acid (LPA) is a bioactive lysophospholipid present in low concentrations in serum and biological fluids but in high concentrations at sites of inflammation. LPA evokes a variety of cellular responses via binding to and activation of its specific G protein-coupled receptors (GPCR), namely LPA1-6. Even though LPA is a chemoattractant for inflammatory cells in vitro, such a role for LPA in vivo remains largely unexplored. In the present study, we used the murine air pouch model to study LPA-mediated leukocyte recruitment in vivo using selective LPA receptor agonist/antagonist and LPA3-deficient mice. We report that 1 ) LPA injection into the air pouch induced leukocyte recruitment and that both LPA1 and LPA3 were involved in this process; 2 ) LPA stimulated the release of the pro-inflammatory chemokines keratinocyte-derived chemokine (KC) and interferon-inducible protein-10 (IP-10) in the air pouch; 3 ) tumor necrosis factor-α (TNF-α) injected into the air pouch prior to LPA strongly potentiated LPA-mediated secretion of cytokines/chemokines, including KC, IL-6, and IP-10, which preceded the enhanced leukocyte influx; and 4 ) blocking CXCR2 significantly reduced leukocyte infiltration. We suggest that LPA, via LPA1 and LPA3 receptors, may play a significant role in inducing and/or sustaining the massive infiltration of leukocytes during inflammation.
关键词：inflammation ; murine air pouch model ; LPA receptor agonist/antagonist ; LPA receptor deficient mice ; CXC chemokines
