Eur Surg Res 2004;36:331–337
(DOI:10.1159/000081641)

Attenuation of Leukocyte Sequestration by Selective Blockade of PECAM-1 or VCAM-1 in Murine Endotoxemia

Nolte D.a,b · Kuebler W.b,c · Muller W.d · Wolff K.a · Messmer K.b
aDepartment of Oral and Maxillofacial Surgery – Regional Plastic Surgery, Knappschaftskrankenhaus Bochum-Langendreer, University of Bochum, Bochum, bInstitute for Surgical Research, Ludwig Maximilian University of Munich, Munich, and cInstitute of Physiology, Charité – Universitätsmedizin Berlin, Berlin, Germany; dDepartment of Pathology and Laboratory Medicine, Weill Medical College, New York, N.Y., USA
email Corresponding Author


 goto top of outline Key Words

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

 goto top of outline Abstract

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.

Copyright © 2004 S. Karger AG, Basel


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 goto top of outline Author Contacts

Dirk Nolte, MD, DDS, PhD
Department of Oral and Maxillofacial Surgery – Regional Plastic Surgery
University Clinic at the Ruhr University of Bochum, In der Schornau 23–25
DE–44892 Bochum (Germany)
Tel. +49 234 299 3502/12, Fax +49 234 299 3509, E-Mail dirk.nolte@ruhr-uni-bochum.de


 goto top of outline Article Information

Received: May 26, 2004
Accepted after revision: June 25, 2004
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 0, Number of References : 38


 goto top of outline Publication Details

European Surgical Research (Clinical and Experimental Surgery)

Vol. 36, No. 6, Year 2004 (Cover Date: November-December 2004)

Journal Editor: K. Messmer, Munich
ISSN: 0014–312X (print), 1421–9921 (Online)

For additional information: http://www.karger.com/esr


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