Attenuation of leukocyte sequestration by selective blockade of PECAM-1 or VCAM-1 in murine endotoxemia

D. Nolte*, W. M. Kuebler, W. A. Muller, K. D. Wolff, K. Messmer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background: Molecular mechanisms regulating leukocyte sequestration into the tissue during endotoxemia and/or sepsis are still poorly understood. This in vivo study investigates the biological role of murine PECAM-1 and VCAM-1 for leukocyte sequestration into the lung, liver and striated skin muscle. Methods: Male BALB/c mice were injected intravenously with murine PECAM-1 IgG chimera or monoclonal antibody (mAb) to VCAM-1 (3 mg/kg body weight); controls received equivalent doses of IgG2a (n = 6 per group). Fifteen minutes thereafter, 2 mg/kg body weight of Salmonella abortus equi endotoxin was injected intravenously. At 24 h after the endotoxin challenge, lungs, livers and striated muscle of skin were analyzed for their myeloperoxidase activity. To monitor intravital leukocyte-endothelial cell interactions, fluorescence videomicroscopy was performed in the skin fold chamber model of the BALB/c mouse at 3, 8 and 24 h after injection of endotoxin. Results: Myeloperoxidase activity at 24 h after the endotoxin challenge in lungs (12,171 ± 2,357 mU/g tissue), livers (2,204 ± 238 mU/g) and striated muscle of the skin (1,161 ± 110 mU/g) was significantly reduced in both treatment groups as compared to controls, with strongest attenuation in the PECAM-1 IgG treatment group. Arteriolar leukocyte sticking at 3 h after endotoxin (230 ± 46 cells × mm-2) was significantly reduced in both treatment groups. Leukocyte sticking in postcapillary venules at 8 h after endotoxin (343 ± 69 cells/mm2) was found reduced only in the VCAM-1-mAb-treated animals (215 ± 53 cells/mm2), while it was enhanced in animals treated with PECAM-1 IgG (572 ± 126 cells/mm2). Conclusion: These data show that both PECAM-1 and VCAM-1 are involved in endotoxin-induced leukocyte sequestration in the lung, liver and muscle, presumably through interference with arteriolar and/or venular leukocyte sticking.

Original languageEnglish (US)
Pages (from-to)331-337
Number of pages7
JournalEuropean Surgical Research
Issue number6
StatePublished - 2004


  • Adhesion molecules
  • Leukocyte-endothelial cell interaction
  • Microcirculation
  • Platelet-endothelial cell adhesion molecule 1
  • Salmonella abortus equi endotoxin
  • Vascular cell adhesion molecule 1

ASJC Scopus subject areas

  • Surgery


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