Faculty Collaboration Database

PECAM-1 dampens cytokine levels during LPS-induced endotoxemia by regulating leukocyte trafficking. Life Sci 2012 Jan 30;90(5-6):177-84

Date

11/29/2011

Pubmed ID

22119535

Pubmed Central ID

PMC3264774

DOI

10.1016/j.lfs.2011.11.002

Scopus ID

2-s2.0-84856097476 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

AIMS: To investigate the mechanism by which platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31), an immunoglobulin (Ig)-superfamily cell adhesion and signaling receptor, regulates pro-inflammatory cytokine levels. The purpose of the present investigation was to test the hypothesis that PECAM-1 influences circulating cytokine levels by regulating the trafficking of activated, cytokine-producing leukocytes to sites of inflammation.

MAIN METHODS: PECAM-1+/+ and PECAM-1-/- mice were subjected to lipopolysaccharide (LPS)-induced endotoxemia, and systemic cytokine levels were measured by Bioplex multiplex cytokine assays. Flow cytometry was employed to enumerate leukocytes at inflammatory sites and to measure cytokine synthesis in leukocyte sub-populations. Enzyme-linked immunosorbent assay (ELISA) was used to measure cytokine levels in tissue samples and in supernatants of in vitro-stimulated leukocytes.

KEY FINDINGS: We confirmed earlier reports that mice deficient in PECAM-1 had greater systemic levels of pro-inflammatory cytokines following intraperitoneal (IP) LPS administration. Interestingly, expression of PECAM-1, in mice, had negligible effects on the level of cytokine synthesis by leukocytes stimulated in vitro with LPS and in peritoneal macrophages isolated from LPS-injected mice. There was, however, excessive accumulation of macrophages and neutrophils in the lungs of PECAM-1-deficient, compared with wild-type, mice--an event that correlated with a prolonged increase in lung pro-inflammatory cytokine levels.

SIGNIFICANCE: Our results demonstrate that PECAM-1 normally functions to dampen systemic cytokine levels during LPS-induced endotoxemia by diminishing the accumulation of cytokine-producing leukocytes at sites of inflammation, rather than by modulating cytokine synthesis by leukocytes.

Author List

Privratsky JR, Tilkens SB, Newman DK, Newman PJ

Authors

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Peter J. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Adhesion
Cell Movement
Chemokine CCL2
Disease Susceptibility
Endotoxemia
Flow Cytometry
Inflammation
Injections, Intraperitoneal
Interleukin-6
Leukocytes
Lipopolysaccharides
Lung
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
Platelet Endothelial Cell Adhesion Molecule-1