Disturbed homeostasis of lung intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 during sepsis.

Abstract

Cecal ligation and puncture (CLP)-induced sepsis in mice was associated with perturbations in vascular adhesion molecules. In CLP mice, lung vascular binding of (125)I-monoclonal antibodies to intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 revealed sharp increases in binding of anti-ICAM-1 and significantly reduced binding of anti-VCAM-1. In whole lung homogenates, intense ICAM-1 up-regulation was found (both in mRNA and in protein levels) during sepsis, whereas very little increase in VCAM-1 could be measured although some increased mRNA was found. During CLP soluble VCAM-1 (sVCAM-1) and soluble ICAM-1 (sICAM-1) appeared in the serum. When mouse dermal microvascular endothelial cells (MDMECs) were incubated with serum from CLP mice, constitutive endothelial VCAM-1 fell in association with the appearance of sVCAM-1 in the supernatant fluids. Under the same conditions, ICAM-1 cell content increased in MDMECs. When MDMECs were evaluated for leukocyte adhesion, exposure to CLP serum caused increased adhesion of neutrophils and decreased adhesion of macrophages and T cells. The progressive build-up in lung myeloperoxidase after CLP was ICAM-1-dependent and independent of VLA-4 and VCAM-1. These data suggest that sepsis disturbs endothelial homeostasis, greatly favoring neutrophil adhesion in the lung microvasculature, thereby putting the lung at increased risk of injury.

• Authors: Ines J Laudes, Ren-Feng Guo, Niels C Riedemann, Cecilia Speyer, Ron Craig, J Vidya Sarma, Peter A Ward
• Journal: The American journal of pathology (Am J Pathol) Vol. 164 Issue 4 Pg. 1435-45 (Apr 2004) ISSN: 0002-9440 [Print] United States
• PMID: 15039231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Peroxidase

Topics

• Animals
• Blotting, Western
• Cell Adhesion (physiology)
• Cells, Cultured
• Endothelial Cells (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Homeostasis (physiology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Leukocytes (physiology)
• Lung (metabolism)
• Male
• Mice
• Peroxidase (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sepsis (physiopathology)
• Vascular Cell Adhesion Molecule-1 (metabolism)