L. Falasca et al., HUMAN KUPFFER CELL RECOGNITION AND PHAGOCYTOSIS OF APOPTOTIC PERIPHERAL-BLOOD LYMPHOCYTES, Experimental cell research, 224(1), 1996, pp. 152-162
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.