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Lymphocyte trafficking through the blood–brain barrier is dependent on endothelial cell heterotrimeric G‐protein signaling
Author(s) -
Adamson Peter,
Wilbourn Barry,
EtienneManneville Sandrine,
Calder Virginia,
Beraud Evelyne,
Milligan Graeme,
Couraud PierreOlivier,
Greenwood John
Publication year - 2002
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/fj.02-0035com
Subject(s) - heterotrimeric g protein , microbiology and biotechnology , pertussis toxin , focal adhesion , signal transduction , biology , g protein , lymphocyte , tyrosine phosphorylation , phosphorylation , immunology
We have previously shown that the engagement of ICAM‐1 on brain endothelial cells (EC) results in the propagation of EC signaling pathways that are necessary for efficient lymphocyte migration across the tight vascular barriers of the brain. Signaling via this receptor alone, however, is unlikely to explain the differential recruitment of leukocytes at different vascular beds. In this study, we investigated the role of EC heterotrimeric G‐protein‐mediated signaling in supporting transendothelial migration of T lymphocytes. Treatment of brain EC monolayers with pertussis toxin (PTX) resulted in ADP‐ribosylation of G‐protein a subunits and inhibition (>80%) of lymphocyte migration without affecting lymphocyte adhesion. Aortic and high endothelial venule EC treated identically resulted in only partial inhibition of lymphocyte migration (<40%). Expression of ribosylation‐resistant (PTX‐insensitive) G‐protein a subunits in brain EC restored their ability to support lymphocyte migration after pretreatment with PTX. Treatment of brain EC with PTX did not inhibit ICAM‐1‐stimulated tyrosine phosphorylation of focal adhesion kinase, suggesting the effects of PTX in inhibiting EC facilitation of lymphocyte migration are distinct from activation of EC through ICAM‐1. We conclude that a heterotrimeric G‐protein‐mediated signaling pathway in brain EC is essential for efficient transendothelial migration of T lymphocytes into the brain.—Adamson, P., Wilbourn, B., Etienne‐Manneville, S.,Calder, V., Beraud, E., Milligan, G., Couraud, P.‐O., Greenwood, J. Lymphocyte trafficking through the blood–brain barrier is dependent on endothelial cell heterotrimeric G‐protein signaling. FASEB J . 16, 1185–1194 (2002)