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Activation of endothelial cell ICAM‐1 stimulates caveolae‐mediated transcytosis
Author(s) -
Hu Guochang,
Vogel Stephen M.,
Visintine David J.,
Malik Asrar B.,
Minshall Richard D.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1166-d
Subject(s) - transcytosis , endocytosis , caveolae , microbiology and biotechnology , phosphorylation , tyrosine phosphorylation , caveolin 1 , proto oncogene tyrosine protein kinase src , transcellular , paracellular transport , chemistry , biology , signal transduction , biochemistry , cell , permeability (electromagnetism) , membrane
Albumin is the primary anti‐oxidant of the interstitium, and thus albumin permeability is a potentially important regulatory mechanism of vascular inflammation. We tested whether ligation of ICAM‐1 in endothelial cells (EC) by activated polymorphonuclear neutrophils (PMN) or ICAM‐1 Ab affects albumin endocytosis and transcytosis by enhancing Src‐dependent phosphorylation of caveolin‐1 (Cav‐1). The addition of formyl‐Met‐Leu‐Phe (fMLP)‐activated PMN to EC for 30 min induced a marked increase in the uptake and transcellular transport of 125 I‐albumin. This response was associated with a pronounced increase in Src Y416 and Cav‐1 Y14 phosphorylation. Cyclodextrin treatment to disrupt caveolae blocked the PMN‐induced increase in endocytosis and transcytosis as did treatment with PP2, a Src ‐family kinase inhibitor, or stable expression of phosphorylation‐defective Cav‐1 mutant, Y14F. Pretreatment of ECs with an ICAM‐1 blocking antibody abolished the increase in Src activation, Cav‐1 phosphorylation, and albumin endocytosis and transcytosis induced by activated PMN. ICAM‐1 activation via Ab crosslinking stimualated Src and Cav‐1 phosphorylation and mimicked the PMN‐induced increase in albumin endocytosis. Increased expression of ICAM‐1 induced by TNFα further promoted Src phosphorylation of Cav‐1 and 125 I‐albumin endocytosis. These data indicate that activation of endothelial cell ICAM‐1 and resultant stimulaiton of caveolae‐mediated transcellular transport may be an important regulatory mechanism of vascular barrier maintenance, subendothelial delivery of blood plasma constituents, and innate immunity.