IQGAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia

Bhattacharya M, Su G, Su X, Oses-Prieto JA, Li JT, Huang X, Hernandez H, Atakilit A, Burlingame AL, Matthay MA, Sheppard D. IQGAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia. Am J Physiol Lung Cell Mol Physiol 303: L12-L19, 2012. First published May 4, 2012; doi:10.1152/ajplung.00375.2011.-We recently reported that integrin alpha v beta(3) is necessary for vascular barrier protection in mouse models of acute lung injury and peritonitis. Here, we used mass spectrometric sequencing of integrin complexes to isolate the novel beta(3)-integrin binding partner IQGAP1. Like integrin beta(3), IQGAP1 localized to the endothelial cell-cell junction after sphingosine-1-phosphate (S1P) treatment, and IQGAP1 knockdown prevented cortical actin formation and barrier enhancement in response to S1P. Furthermore, knockdown of IQGAP1 prevented localization of integrin alpha v beta(3) to the cell-cell junction. Similar to beta(3)-null animals, IQGAP1-null mice had increased pulmonary vascular leak compared with wild-type controls 3 days after intratracheal LPS. In an Escherichia coli pneumonia model, IQGAP1 knockout mice had increased lung weights, lung water, and lung extravascular plasma equivalents of I-125-labeled albumin compared with wild-type controls. Taken together, these experiments indicate that IQGAP1 is necessary for S1P-mediated vascular barrier protection during acute lung injury and is required for junctional localization of the barrier-protective integrin alpha v beta(3).