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Genetic blockade of JAM‐A‐ and PECAM‐1‐dependent pathways does not lead to an additive inhibitory effect on leukocyte transmigration
Author(s) -
Woodfin Abigail,
Reichel Christoph,
Khandoga Andrej,
Corada Monica,
Haskard Dorian,
Dejana Elisabetta,
Krombach Fritz,
Nourshargh Sussan
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.20.4.a648-b
Subject(s) - intravital microscopy , blockade , microbiology and biotechnology , inflammation , chemistry , biology , immunology , receptor , biochemistry , genetics , in vivo
JAM‐A and PECAM‐1 have been implicated in leukocyte transmigration. However, whilst PECAM‐1 appears to mediate this response via a homophilic interaction between leukocyte and endothelial cell (EC) PECAM‐1, current literature indicates that depending on the inflammatory model employed, leukocyte or EC JAM‐A may play an important role in leukocyte transmigration. We aimed to further address this issue and also investigated the effect of blocking both PECAM‐1‐ and JAM‐A‐dependent pathways in leukocyte transmigration. Fluorescently‐labelled murine leukocytes isolated from wild‐type (WT) or JAM‐A KO donors exhibited similar level of transmigration through WT IL‐1β‐stimulated cremasteric venules (4hr test period), as observed by intravital microscopy. In the same model, WT leukocytes exhibited a significant reduction in transmigration in JAM‐A KO mice (53 % inhibition, p<0.01), collectively indicating a role for EC but not leukocyte JAM‐A. Furthermore, a similar level of leukocyte transmigration was noted when leukocytes isolated from PECAM‐1 KO mice were injected into WT or JAM‐A KO animals (44 %, and 48 % inhibition respectively), suggesting that within the protocol employed, genetic blockade of PECAM‐1‐ and JAM‐A‐dependent pathways does not lead to an enhanced suppression of leukocyte transmigration. Supported by EU Network of Excellence ‘MAIN’ (LSHG‐CT‐2003‐502935)