NDLI: The role of endothelial PI3Kγ activity in neutrophil trafficking

Content Provider	PubMed Central
Author	Puri, Kamal D. Doggett, Teresa A. Huang, Ching-yu Jason, Douangpanya Hayflick, Joel S. Turner, Martin Penninger, Josef Diacovo, Thomas G.
Copyright Year	2005
Abstract	Phosphoinositide 3-kinase gamma (PI3Kγ) in neutrophils plays a critical role in the directed migration of these cells into inflamed tissues. In this study, we demonstrate the importance of the endothelial component of PI3Kγ activity relative to its leukocyte counterpart in supporting neutrophil interactions with the inflamed vessel wall. Despite the reconstitution of class-Ib PI3K function in neutrophils of p110γ–/– mice, we observed a 45% reduction in accumulation of these cells in an acute lung injury model. Mechanistically, this appears to result from a perturbation in selectin-mediated adhesion as manifested by a 70% reduction in wild-type (WT) neutrophil attachment to and 17-fold increase in rolling velocities on p110γ–/– microvessels in vivo in response to tumor necrosis factor alpha (TNFα). This alteration in adhesion was further augmented by a deficiency in p110δ, suggesting that the activity of both catalytic subunits is required for efficient capture of neutrophils by cytokine-stimulated endothelium. Interestingly, E-selectin–mediated adhesion in p110γ–/– mice was impaired by more than 95%, but no defect in nuclear factor kappa B (NF-κB)–induced gene expression was observed. These findings suggest a previously unrecognized partnership between class-I PI3Ks expressed in leukocytes and endothelium, the combination of which is required for the efficient trafficking of immunocompetent cells to sites of inflammation.
Related Links	http://dx.doi.org/10.1182/blood-2005-01-0023
Ending Page	157
Page Count	8
Starting Page	150
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	1
Volume Number	106
Language	English
Publisher	The American Society of Hematology
Publisher Date	2005-03-01
Access Restriction	Open
Rights Holder	The American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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