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Publication
Macrophage-dependent neutrophil recruitment is impaired under conditions of
increased intestinal permeability in JAM-A-deficient mice.
Authors Luissint AC, Williams HC, Kim W, Flemming S, Azcutia V, Hilgarth RS, Leary MNO,
Denning TL, Nusrat A, Parkos CA
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal Mucosal immunology
Year 2019
Date Published 5/1/2019
Volume : Pages 12 : 668 - 678
PubMed Reference 30745566
Abstract Junctional adhesion molecule-A (JAM-A) is a transmembrane glycoprotein expressed
on leukocytes, endothelia, and epithelia that regulates biological processes
including barrier function and immune responses. While JAM-A has been reported
to facilitate tissue infiltration of leukocytes under inflammatory conditions,
the contributions of leukocyte-expressed JAM-A in vivo remain unresolved. We
investigated the role of leukocyte-expressed JAM-A in acute peritonitis induced
by zymosan, lipopolysaccharide (LPS), or TNFa using mice with selective loss of
JAM-A in myelomonocytic cells (LysM-Cre;Jam-afl/fl). Surprisingly, in
LysM-Cre;Jam-afl/fl mice, loss of JAM-A did not affect neutrophil (PMN)
recruitment into the peritoneum in response to zymosan, LPS, or TNFa although it
was significantly reduced in Jam-aKO mice. In parallel, Jam-aKO peritoneal
macrophages exhibited diminished CXCL1 chemokine production and decreased
activation of NF-kB, whereas those from LysM-Cre;Jam-afl/fl mice were
unaffected. Using Villin-Cre;Jam-afl/fl mice, targeted loss of JAM-A on
intestinal epithelial cells resulted in increased intestinal permeability along
with reduced peritoneal PMN migration as well as lower levels of CXCL1 and
active NF-kB similar to that observed in Jam-aKO animals. Interestingly, in
germ-free Villin-Cre;Jam-afl/fl mice, PMN recruitment was unaffected suggesting
dependence on gut microbiota. Such observations highlight the functional link
between a leaky gut and regulation of innate immune responses.




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