Phosphoinositide 3-kinase γ required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung
Reutershan J, Saprito MS, Wu D, Rueckle T, Ley K (2010)
Publication Type: Journal article
Publication year: 2010
Journal
Book Volume: 35
Pages Range: 1137-1147
Journal Issue: 5
DOI: 10.1183/09031936.00085509
Abstract
Phosphoinositide 3-kinase γ(PI3Kγ) is a critical mediator of directional cell movement. Here, we sought to characterise the role of PI3Kγ in mediating the different steps of polymorphonuclear leukocyte (PMN) trafficking in the lung. In a murine model of lipopolysaccharide (LPS)-induced lung injury, PMN migration into the different lung compartments was determined in PI3Kγ gene-deficient (PI3Kγ-/-) and wild-type mice. Bone marrow chimeras were created to characterise the role of PI3Kγ on haematopoietic versus nonhaematopoietic cells. A small-molecule PI3Kγ inhibitor was tested in vitro and in vivo. PMN adhesion to the pulmonary endothelium and transendothelial migration into the lung interstitium was enhanced in PI3Kγ-/-mice. However, transepithelial migration into the alveolar space was reduced in these mice. When irradiated PI3Kγ-/- mice were reconstituted with bone marrow from wild-type mice, migratory activity into the alveolar space was restored partially. A small-molecule PI3Kγ inhibitor reduced chemokine-induced PMN migration in vitro when PMNs or epithelial cells, but not when endothelial cells, were treated. The inhibitor also reduced LPS-induced PMN migration in vivo. We conclude that PI3Kγ is required for transepithelial but not for transendothelial migration in LPS-induced lung injury. Inhibition of PI3Kγ activity may be effective at curbing excessive PMN infiltration in lung injury. Copyright©ERS Journals Ltd 201.
Authors with CRIS profile
Involved external institutions
University of Virginia (UVA)
United States (USA) (US)
Yale University
United States (USA) (US)
Merck Serono S.A.
Switzerland (CH)
Eberhard Karls Universität Tübingen
Germany (DE)
United States (USA) (US)
Yale University
United States (USA) (US)
Merck Serono S.A.
Switzerland (CH)
Eberhard Karls Universität Tübingen
Germany (DE)
How to cite
APA:
Reutershan, J., Saprito, M.S., Wu, D., Rueckle, T., & Ley, K. (2010). Phosphoinositide 3-kinase γ required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung. European Respiratory Journal, 35(5), 1137-1147. https://dx.doi.org/10.1183/09031936.00085509
MLA:
Reutershan, J., et al. "Phosphoinositide 3-kinase γ required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung." European Respiratory Journal 35.5 (2010): 1137-1147.
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