Caveolin-1 expression determines the route of neutrophil extravasation through skin microvasculature.
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.
Marmon
Shana
S
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
Hinchey
Joseph
J
Oh
Philmo
P
Cammer
Michael
M
de Almeida
Cecilia J
CJ
Gunther
Leslie
L
Raine
Cedric S
CS
Lisanti
Michael P
MP
D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000276:immunology
D051242:Caveolin 1; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1