* Vascular Research Division, Departments of Pathology, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts;
Washington University School of Medicine, St. Louis, Missouri;
Department of Dermatology, Kyoto University, Japan; and
Institute of Cell Biology, University of Münster, Germany
Correspondence: Francis W. Luscinskas, Ph.D., Vascular Research Division, Brigham & Women’s Hospital, 221 Longwood Ave., LMRC 414a, Boston, MA 02115. E-mail: fluscinskas{at}rics.bwh.harvard.edu
Recent evidence has suggested a role for neutrophil proteases during certain inflammatory responses. We demonstrated previously that neutrophil proteases can degrade components of the adherens junctions during neutrophil-endothelial adhesion. We tested the hypothesis that degradation of VE-cadherin at lateral junctions by elastase or MMP-9 facilitates neutrophil transendothelial migration. Neutrophils from MMP-9 or elastase null mice and strain-matched control mice expressed high levels of LFA-1, Mac-1, and L-selectin on their cell surface. Under flow conditions, wild-type and deficient neutrophils rolled, arrested, and transmigrated activated murine endothelium. There was no difference in the total numbers of interacting neutrophils or in the percentage of transmigrated cells. In addition, deficient neutrophils remained capable of degrading murine endothelial VE-cadherin. These results indicate that although neutrophil proteases may play a role in the acute inflammatory response, neutrophil elastase or MMP-9 is not essential for neutrophil transendothelial migration in this murine system.
Key Words: inflammation • protease • leukocyte • endothelium
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