Abstract Cell surface expression of carbohydrate recep- tors (i.e. mannose and galactose receptors) and phagocy- tosis of apoptotic cells by sinusoidal liver cells was stud- ied. Binding sites and phagocytic activity were quanti- fied at different time intervals (1, 3, 5, 7, 9, 11, 13, 15, 20, 30, 40 and 60 days) after the in vivo administration to rats of a potent liver mitogen, lead nitrate, that also in- duces apoptosis. The number and distribution of binding sites was receptor and cell-type dependent during the days following the metal injection. The use of competing saccharides in inhibition uptake experiments suggests that sinusoidal liver cells actively phagocytose apoptotic hepatocytes and circulating apoptotic cells by using both receptors. In particular, Kupffer cells at 5 and 15 days af- ter the lead nitrate injection are very active in internaliz- ing apoptotic cells (two- to threefold control). However, phagosomes containing apoptotic hepatocytes are often seen inside the cytoplasm of parenchymal and endotheli- al cells. Key words Liver cells · Galactose-specific receptor · Mannose-specific receptor · Apoptosis · Rat (Wistar) Introduction Phagocytosis, one of the functions of the liver, is a prop- erty of the sinusoidal (i.e. endothelial and Kupffer) cells (Smedsrod et al. 1990; Toth and Thomas 1992). Endo- thelial and Kupffer cells perform many functions that are essential for the maintenance of homeostasis, and endo- cytosis is a major route for transport of proteins or gly- coconjugate ligands into liver cells (Steinman et al. 1983). It is essential for the removal from the blood not only of plasma proteins but also of particulate material such as apoptotic cells (Dini et al. 1996). Apoptotic cells and/or bodies are produced at the end point of the apo- ptotic process, the active, genetically regulated mode of cell death observed in physiological conditions (e.g. re- gression of embryonic structures) and also in response to cell damage (e.g. response to antitumoral drugs, heat shock, oxidative stress) (Clarke 1990; Cohen 1993; Kerr et al. 1995; Payne et al. 1995). A key factor in the programme of events associated with cell death is the efficient recognition and removal by neighbouring viable cells of cells which have under- gone apoptosis (Savill et al. 1993; Dini et al. 1996). The fact that dead cells are also ingested by neighbouring vi- able cells during development suggests that this process serves a fundamental homeostatic role in multicellular organisms (Ellis et al. 1991). Failure to recognize and re- move apoptotic cells could lead to secondary necrosis of the apoptotic cells with the consequent release of poten- tially noxious substances. Therefore, the removal of apo- ptotic cells/bodies prior to necrosis would serve to limit the potential for inflammatory reactions and possibly the development of autoimmune responses (Dini et al. 1996; Meagher et al. 1992; Savill et al. 1993; Stern et al. 1992). The recognition mechanisms that act as receptors on the phagocytosing cells are beginning to be defined. Al- ternative mechanisms for removal of apoptotic cells by phagocytes have been reported and are related to the cell type and system used (Dini et al. 1996; Ellis et al. 1991; Meagher et al. 1992; Savill et al. 1993). Human-mono- cyte-derived macrophages utilize the vitronectin recep- tor, thrombospondin and CD36 (Ren et al. 1995; Savill et al. 1990); macrophages and non-professional phagocytes recognize phosphatidylserine expressed on the apoptotic cells’ surface (Fadok et al. 1992a, 1992b); 61D3 antigen has a role in recognition of apoptotic B cells (Flora and This study was supported by grants from Consiglio Nazionale delle Ricerche Progetto Strategico “Proliferazione ed Apoptosi” and by Ministero dell’Universita’ e della Ricerca Scientifica e Tecnologica (MURST). M. Ruzittu · E.C. Carlá · M.R. Montinari · L. Dini ( ✉ ) Department of Biology, University of Lecce, Strada per Monteroni, I-73100 Lecce, Italy e-mail: ldini@ilenic.unile.it; Tel: +39 832 320614; Fax: +39 832 320626 G. Maietta Laboratorio Pignatelli, I-73100 Lecce, Italy Cell Tissue Res (1999) 298:105–112 © Springer-Verlag 1999 Digital Object Identifier (DOI) 10.1007/s004419900059 REGULAR ARTICLE M. Ruzittu · E.C. Carlá · M.R. Montinari G. Maietta · L. Dini Modulation of cell surface expression of liver carbohydrate receptors during in vivo induction of apoptosis with lead nitrate Received: 7 July 1998 / Accepted: 1 May 1999 / Published online: 10 August 1999