CD44, alpha(4) integrin, and fucoidin receptor-mediated phagocytosis of apoptotic leukocytes.
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 alpha4 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.
Johnson
Jacob D
JD
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267-0529, USA.
Hess
Krista L
KL
Cook-Mills
Joan M
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D039441:Integrin alpha4 / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology* / Q000502:physiology*; D008351:Mannans / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009336:Necrosis; D010587:Phagocytosis; D011134:Polysaccharides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018960:Hyaluronan Receptors; D008351:Mannans; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D039441:Integrin alpha4; C007789:fucoidan