Endothelial cell PECAM-1 confers protection against endotoxic shock

Matthias Maas, Michelle Stapleton, Carmen Bergom, David L. Mattson, Bebra K. Newman, Peter J. Newman

Research output: Contribution to journalArticle

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.

Original languageEnglish (US)
Pages (from-to)H159-H164
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number1 57-1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

CD31 Antigens
Septic Shock
Endothelial Cells
Intercellular Junctions
Thrombosis
Leukocytes
Transendothelial and Transepithelial Migration
Platelet Activation
Cell Adhesion
Endotoxins
Blood Vessels
Cell Death
Blood Platelets
Apoptosis
Inflammation
Mortality

Keywords

  • Endotoxin
  • Platelet endothelial cell adhesion molecule-1
  • Sepsis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Endothelial cell PECAM-1 confers protection against endotoxic shock. / Maas, Matthias; Stapleton, Michelle; Bergom, Carmen; Mattson, David L.; Newman, Bebra K.; Newman, Peter J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 1 57-1, 01.01.2005, p. H159-H164.

Research output: Contribution to journalArticle

Maas, Matthias ; Stapleton, Michelle ; Bergom, Carmen ; Mattson, David L. ; Newman, Bebra K. ; Newman, Peter J. / Endothelial cell PECAM-1 confers protection against endotoxic shock. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 1 57-1. pp. H159-H164.
@article{18b710a1ab9449b5b3040216398e5229,
title = "Endothelial cell PECAM-1 confers protection against endotoxic shock",
abstract = "Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.",
keywords = "Endotoxin, Platelet endothelial cell adhesion molecule-1, Sepsis",
author = "Matthias Maas and Michelle Stapleton and Carmen Bergom and Mattson, {David L.} and Newman, {Bebra K.} and Newman, {Peter J.}",
year = "2005",
month = "1",
day = "1",
doi = "10.1152/ajpheart.00500.2004",
language = "English (US)",
volume = "288",
pages = "H159--H164",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 57-1",

}

TY - JOUR

T1 - Endothelial cell PECAM-1 confers protection against endotoxic shock

AU - Maas, Matthias

AU - Stapleton, Michelle

AU - Bergom, Carmen

AU - Mattson, David L.

AU - Newman, Bebra K.

AU - Newman, Peter J.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.

AB - Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.

KW - Endotoxin

KW - Platelet endothelial cell adhesion molecule-1

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=11144278572&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144278572&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00500.2004

DO - 10.1152/ajpheart.00500.2004

M3 - Article

C2 - 15319204

AN - SCOPUS:11144278572

VL - 288

SP - H159-H164

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1 57-1

ER -