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PGE2 Signaling Triggers PECAM-Indepe...

Hayashi, Vanessa Sayuri,

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PGE2 Signaling Triggers PECAM-Independent Transendothelial Migration In Vitro and In Vivo /

Record Type:	Electronic resources : Monograph/item
Title/Author:	PGE2 Signaling Triggers PECAM-Independent Transendothelial Migration In Vitro and In Vivo // Vanessa Sayuri Hayashi.
Author:	Hayashi, Vanessa Sayuri,
Description:	1 electronic resource (137 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
Contained By:	Dissertations Abstracts International86-12B.
Subject:	Pathology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=32038002
ISBN:	9798315797739

PGE2 Signaling Triggers PECAM-Independent Transendothelial Migration In Vitro and In Vivo /
Hayashi, Vanessa Sayuri,

PGE2 Signaling Triggers PECAM-Independent Transendothelial Migration In Vitro and In Vivo /Vanessa Sayuri Hayashi. - 1 electronic resource (137 pages)

Source: Dissertations Abstracts International, Volume: 86-12, Section: B.

Genetic deletion or antibody blockade of platelet endothelial cell adhesion molecule-1 (PECAM, CD31) inhibits transendothelial migration (TEM) of leukocytes in all mouse strains studied except C57BL/6. Previously, we showed that this phenotype maps to a single 35.8 Mb locus on mouse chromosome 2, that contains the genes Ptgs1, Ptges, and Ptges2, which encode key enzymes involved in the Prostaglandin E2 (PGE2) synthesis pathway. PGE2 is a pro-inflammatory lipid mediator that binds four E prostanoid receptors (EP1-4). We hypothesized that PGE2 signaling supports TEM via a PECAM-independent mechanism. In vitro TEM assays demonstrate that PGE2 or 16,16-dimethyl PGE2 can restore transmigration of polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) despite a TEM blockade with anti-PECAM antibody. This pro-transmigratory effect could be blocked with a combination of EP1 and EP3 antagonists, SC-51089 and DG-041, or with transient receptor potential canonical 6 (TRPC6) antagonist, BI-749327. 17-phenyl trinor PGE2, an agonist of EP1 and EP3, also restored transmigration of PMNs blocked with anti-PECAM antibody. In vivo, PGE2 overcame an anti-PECAM blockade when administered to FVB/n mice in thioglycolate peritonitis or croton oil dermatitis models, whereas blocking EP1 with SC-51089 decreased TEM in C57BL/6 PECAM-/- mice. Our findings demonstrate that PGE2 induces of PECAM-independent TEM, and pinpoint EP1 and EP3 as the receptors that relay said signal.

English

ISBN: 9798315797739Subjects--Topical Terms:

643180
Pathology.
Subjects--Index Terms:

Genetic deletion

PGE2 Signaling Triggers PECAM-Independent Transendothelial Migration In Vitro and In Vivo /
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520 $a Genetic deletion or antibody blockade of platelet endothelial cell adhesion molecule-1 (PECAM, CD31) inhibits transendothelial migration (TEM) of leukocytes in all mouse strains studied except C57BL/6. Previously, we showed that this phenotype maps to a single 35.8 Mb locus on mouse chromosome 2, that contains the genes Ptgs1, Ptges, and Ptges2, which encode key enzymes involved in the Prostaglandin E2 (PGE2) synthesis pathway. PGE2 is a pro-inflammatory lipid mediator that binds four E prostanoid receptors (EP1-4). We hypothesized that PGE2 signaling supports TEM via a PECAM-independent mechanism. In vitro TEM assays demonstrate that PGE2 or 16,16-dimethyl PGE2 can restore transmigration of polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) despite a TEM blockade with anti-PECAM antibody. This pro-transmigratory effect could be blocked with a combination of EP1 and EP3 antagonists, SC-51089 and DG-041, or with transient receptor potential canonical 6 (TRPC6) antagonist, BI-749327. 17-phenyl trinor PGE2, an agonist of EP1 and EP3, also restored transmigration of PMNs blocked with anti-PECAM antibody. In vivo, PGE2 overcame an anti-PECAM blockade when administered to FVB/n mice in thioglycolate peritonitis or croton oil dermatitis models, whereas blocking EP1 with SC-51089 decreased TEM in C57BL/6 PECAM-/- mice. Our findings demonstrate that PGE2 induces of PECAM-independent TEM, and pinpoint EP1 and EP3 as the receptors that relay said signal.
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650 4 $a Immunology. $3 611031
650 4 $a Cellular biology. $3 3172791
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653 $a TRPC6 antagonist
653 $a EP3 antagonists
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710 2 $a Northwestern University. $b Driskill Graduate Training Program in Life Sciences. $e degree granting institution. $3 3827178
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720 1 $a Green, Kathleen J. $e degree supervisor.
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