HUMAN KUPFFER CELL RECOGNITION AND PHAGOCYTOSIS OF APOPTOTIC PERIPHERAL-BLOOD LYMPHOCYTES

Citation
L. Falasca et al., HUMAN KUPFFER CELL RECOGNITION AND PHAGOCYTOSIS OF APOPTOTIC PERIPHERAL-BLOOD LYMPHOCYTES, Experimental cell research, 224(1), 1996, pp. 152-162
Citations number
35
Categorie Soggetti
Oncology,"Cell Biology
Journal title
ISSN journal
00144827
Volume
224
Issue
1
Year of publication
1996
Pages
152 - 162
Database
ISI
SICI code
0014-4827(1996)224:1<152:HKCRAP>2.0.ZU;2-B
Abstract
Cells undergoing apoptosis are recognized and rapidly phagocytosed by macrophages before their degradation, thus preventing the inflammatory reaction and protecting tissues from the damaging effects of released potentially harmful intracellular contents, In spite of growing inter est in the mechanisms leading to the engulfment of apoptotic cells, th e molecular bases by which an apoptotic cell is recognized are not ent irely understood. Among the several potential mechanisms by which a ma crophage can identify a cell as apoptotic, the data reported in the pr esent paper support the idea that Kupffer cells phagocytose apoptotic cells by means of lectin-like receptors. Human Kupffer cells, which po ssess galactose-specific binding sites, can recognize and phagocytose peripheral blood lymphocytes undergoing apoptosis after heat shock (43 degrees C) or cycloheximide treatment, but not normal living peripher al blood lymphocytes. The putative structure by which apoptotic pherip heral blood lymphocytes are targeted as ''edible'' could be the molecu lar changes in the plasma membrane. In fact, our experiments indicate that the membranes of apoptotic peripheral blood lymphocytes express i ncreased amounts of N-acetylgalactosamine, D-galactose, and mannose re sidues when compared with membranes of normal PBL. Phagocytosis was in hibited by adding to the culture medium sugar cocktail solution (gluco se, N-acetylgalactosamine, methyl mannopyranoside, fucose, 80 mM final concentration) or 60 a lower extent by desialylated glycoproteins (la ctosylated bovine serum albumin, asialofetuin, 2 mg/ml final concentra tion), but not by nondesialylated glycoproteins (fetuin, 2 mg/ml final concentration, bovine serum albumin, 20% final concentration). In add ition, phagocytosis of apoptotic peripheral blood lymphocytes by human Kupffer cells was a very rapid process, being almost entirely complet ed within 15 min of incubation. (C) 1996 Academic Press, Inc.