• Changsuk Moon, Jeong Ran Han, Hyun-Jung Park, Jong Sik Hah, and Jihee Lee Kang.
• Department of Physiology, Division of Cell Biology, Ewha Medical Research Center, School of Medicine, Ewha Womans University, Seoul, Seoul, Korea. 94cmoon@hanmail.net
• Resp Res. 2009 Jan 1;10:18.

BackgroundSynthetic peptides containing the RGD sequence inhibit integrin-related functions in different cell systems. Here, we investigated the effects of synthetic Arg-Gly-Asp-Ser (RGDS) peptide on key inflammatory responses to intratracheal (i.t.) lipopolysaccharide (LPS) treatment and on the integrin signaled mitogen-activated protein (MAP) kinase pathway during the development of acute lung injury.MethodsSaline or LPS (1.5 mg/kg) was administered i.t. with or without a single dose of RGDS (1, 2.5, or 5 mg/kg, i.p.), anti-alphav or anti-beta3 mAb (5 mg/kg, i.p.). Mice were sacrificed 4 or 24 h post-LPS.ResultsA pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-alpha and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL) fluid at 4 or 24 h post-LPS treatment. RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue. Importantly, the inhibition of the inflammatory responses and the kinase pathways were still evident when this peptide was administered 2 h after LPS treatment. Similarly, a blocking antibody against integrin alphav significantly inhibited LPS-induced inflammatory cell migration into the lung, protein accumulation and proinflammatory mediator production in BAL fluid, at 4 or 24 h post-LPS. Anti-beta3 also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS.ConclusionThese results suggest that RGDS with high specificity for alphavintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.

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