ICAM-1 and VCAM-1 mediate endotoxemic myocardial dysfunction independent of neutrophil accumulation.
Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in neutrophil-mediated lung and liver injury during sepsis. However, the role of these adhesion molecules as well as the contribution of neutrophils in myocardial dysfunction during sepsis remains to be determined. The purpose of this study was to examine the role of ICAM-1, VCAM-1, and neutrophils in lipopolysaccharide (LPS)-induced myocardial dysfunction. Mice were subjected to LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by nearly 40% at 6 h after LPS. Immunofluorescent staining revealed a temporal increase in myocardial ICAM-1/VCAM-1 expression and neutrophils after LPS. Antibody blockade of VCAM-1 reduced myocardial neutrophil accumulation and abrogated LPS-induced cardiac dysfunction. Antibody blockade or absence of ICAM-1 (gene knockout) also abrogated LPS-induced cardiac dysfunction but did not reduce neutrophil accumulation. Neutrophil depletion (vinblastine or antibody) did not protect from LPS-induced myocardial dysfunction. Our results suggest that although endotoxemic myocardial dysfunction requires both ICAM-1 and VCAM-1, it occurs independent of neutrophil accumulation.
Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. christopher.raeburn@uchsc.edu
Christopher D
CD
Raeburn
Casey M
CM
Calkins
Michael A
MA
Zimmerman
Yong
Y
Song
Lihua
L
Ao
Anirban
A
Banerjee
Alden H
AH
Harken
Xianzhong
X
Meng
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002452:Cell Count; D004195:Disease Models, Animal; D018450:Disease Progression; D019446:Endotoxemia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic; D008070:Lipopolysaccharides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014747:Vinblastine