Premium
Intracellular signals mediated by crosslinking Monocyte PECAM promote transendothelial migration in the presence of a transmigration blockade
Author(s) -
Florey Oliver,
Muller William
Publication year - 2008
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.22.1_supplement.166.3
Subject(s) - microbiology and biotechnology , intracellular , monocyte , tyrosine phosphorylation , tyrosine kinase , phosphorylation , chemistry , biology , signal transduction , immunology
PECAM is known to play an important role in the transmigration of leukocytes across the endothelium, yet the molecular mechanisms behind this process remain to be elucidated, particularly regarding PECAM on the leukocyte. Inhibiting the homophilic interaction between leukocyte PECAM and endothelial PECAM using blocking antibodies has been shown to reduce leukocyte transmigration. Using an in vitro system, we show that we can overcome a block of transmigration mediated by either anti‐PECAM or anti‐CD99 by cross‐linking PECAM on the surfaces of the arrested monocytes. Crosslinking CD99, another protein involved in monocyte transmigration, did not reverse the inhibition. We found no evidence of a soluble factor released from leukocytes that may explain these results, as pre‐conditioned media from PECAM crosslinked leukocytes did not reverse the transmigration block. This leads us to postulate that crosslinking leukocyte PECAM induces intracellular signals that are important for transmigration and bypasses the requirement for homophilic PECAM interaction. Crosslinking PECAM on monocytes induces a rapid increase in tyrosine phosphorylation of several proteins as well as a src and tyrosine kinase‐dependent increase in intracellular calcium and F‐actin content. This is the first evidence that leukocyte PECAM plays an active role in transmigration beyond the requirement for homophilic engagement.