Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0303092 on August 11, 2003

Published online before print August 11, 2003
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(Journal of Leukocyte Biology. 2003;74:810-820.)
© 2003 by Society for Leukocyte Biology

CD44, {alpha}4 integrin, and fucoidin receptor-mediated phagocytosis of apoptotic leukocytes

Jacob D. Johnson, Krista L. Hess and Joan M. Cook-Mills1

Department of Pathology and Laboratory Medicine, University of Cincinnati, Ohio

1Correspondence: Department of Pathology and Laboratory Medicine, 231 Albert Sabin Way, University of Cincinnati, Cincinnati, OH 45267-0529. E-mail: joan.cook{at}uc.edu

Various types of phagocytes mediate the clearance of apoptotic cells. We previously reported that human and murine high endothelial venule (HEV) cells ingest apoptotic cells. In this report, we examined endothelial cell fucoidin receptor-mediated phagocytosis using a murine endothelial cell model mHEV. mHEV cell recognition of apoptotic leukocytes was blocked by fucoidin but not by other phagocytic receptor inhibitors such as mannose, fucose, N-acetylglucosamine, phosphatidylserine (PS), or blocking anti-PS receptor antibodies. Thus, the mHEV cells used fucoidin receptors for recognition and phagocytosis of apoptotic leukocytes. The fucoidin receptor-mediated endothelial cell phagocytosis was specific for apoptotic leukocytes, as necrotic cells were not ingested. This is in contrast to macrophages, which ingest apoptotic and necrotic cells. Endothelial cell phagocytosis of apoptotic cells did not alter viable lymphocyte migration across these endothelial cells. Antibody blocking of CD44 and {alpha}4 integrin on the apoptotic leukocyte inhibited this endothelial cell phagocytosis, suggesting a novel function for these adhesion molecules in the removal of apoptotic targets. The removal of apoptotic leukocytes by endothelial cells may protect the microvasculature, thus ensuring that viable lymphocytes can successfully migrate into tissues.

Key Words: lectin • carbohydrate • cell adhesion molecules • phosphatidylserine • endothelial cells




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