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(American Journal of Pathology. 2009;174:684-692.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080091

Caveolin-1 Expression Determines the Route of Neutrophil Extravasation through Skin Microvasculature

Shana Marmon*, Joseph Hinchey{dagger}, Philmo Oh{ddagger}, Michael Cammer§, Cecilia J. de Almeida, Leslie Gunther§, Cedric S. Raine|| and Michael P. Lisanti*¶**{dagger}{dagger}

From the Departments of Molecular Pharmacology,* Microbiology and Immunology,{dagger} Anatomy and Structural Biology,§ and Pathology, Neurology and Neuroscience, || Albert Einstein College of Medicine, Bronx, New York; the Department of Molecular Pathogenesis,{ddagger} New York University School of Medicine, New York, New York; the Departments of Cancer Biology and Medical Oncology,{dagger}{dagger} Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center,** Thomas Jefferson University, Philadelphia, Pennsylvania

Interleukin-8 plays a key role in the acute inflammatory response by mediating recruitment of neutrophils through vessel walls into affected tissues. During this process, molecular signals guide circulating blood neutrophils to target specific vessels for extravasation and to migrate through such vessels via particular routes. Our results show that levels of endothelial caveolin-1, the protein responsible for the induction of the membrane domains known as caveolae, are critical to each of these processes. We demonstrate that, in response to the intradermal injection of interleukin-8, neutrophils are preferentially recruited to a unique subset of venules that express high levels of intercellular adhesion molecule-1 and low levels of caveolin-1. Our results show that neutrophils traverse human dermal microvascular endothelial cells using one of two pathways: a transcellular route directly through the cell or a paracellular route through cellular junctions. Caveolin-1 expression appears to favor the transcellular path while down-regulation of caveolin-1 promotes the paracellular route.






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Copyright © 2009 by the American Society for Investigative Pathology.