Molecular immunology
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Molecular immunology · Jan 2010
The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production.
In this work, we show that P2 nucleotide receptors control lipopolysaccharide (LPS)-induced neutrophil migration in the mouse air pouch model. Neutrophil infiltration in LPS-treated air pouches was reduced by the intravenous (iv) administration of the non-selective P2 receptor antagonist PPADS but not by suramin and RB-2. In addition, the iv administration of a P2 receptor ligand, UTP, enhanced LPS-induced neutrophil migration. ⋯ As determined in vitro, PPADS did not affect MIP-2 and KC release from air pouch resident cells nor from accumulated neutrophils. MIP-2 and KC production in the LPS-treated air pouches correlated with an early neutrophil migration (1h after LPS injection), and both of these effects were significantly reduced in mice administered with PPADS. Altogether, these data suggest that P2Y(4) receptor expressed in circulating leukocytes and/or endothelium controls LPS-induced acute neutrophil recruitment in mouse air pouch.