The in situ liver recognition of apoptotic lymphocytes was studied by using different sources of lymphocytes (i.e. human, rat and mouse) and animal models (i.e. rat and mouse). Lymphocytes were induced to apoptosis using 10–2M cycloheximide for up to 24 hours; three types of apoptosing lymphocytes, corresponding to different stages in the apoptotic process, were described: type 1 or early apoptosis, type 2 or mature apoptosis and type 3 or late/necrotic apoptosis. When livers were in situ injected with apoptotic lymphocytes enriched for type 1 (early), 2 (mature) or 3 (late/necrotic) apoptosis, they recognized and internalized apoptosing cells, with an efficiency directly dependent on the stage of the apoptotic process. The highest recognition rate, which was, in all cases, mediated by galactose- and mannose-specific receptors, was obtained with homologous apoptotic cells (i.e. rat lymphocytes and rat liver). Moreover, the drastically reduced efficiency of recognition of human or mouse apoptotic lymphocytes when injected into rat liver, suggested the involvement also of species-specific antigens

No abstract

Background: Apoptosis and its modulation are crucial factors for the maintenance of liver health, allowing hepatocytes to die without provoking a potential harmful inflammatory response through a tightly controlled and regulated process. Since Kupffer cells play a key role in the maintenance of liver function, the aim of this study was to verify whether Kupffer cells are involved in the induction of liver apoptosis after i.v. injection of Pb(NO 3 ) 2 likely by secretion mechanisms.

Modifications of hepatocyte cell surface were determined after single i.v. injection to rats of Pb(NO 3 ) 2 (known to induce liver hyperplasia followed by apoptosis) or GdCl 3 (known to induce proliferation of parenchymal cells and Kupffer cell depletion) or administration of GdCl 3 24 h before Pb(NO 3 ) 2 injection (known to reduce hyperplasia and apoptosis induced in the parenchymal liver cells by the single Pb(NO 3 ) 2 injection). Rats were sacrificed at fixed times after the treatments (1, 3 and 5 days) and hepatocytes were isolated by enzymatic liver perfusion. In spite of the intracellular target of the heavy metals, signals leading to liver hyperplasia and apoptosis (with rates different for the different experimental conditions) were generated, which in turn were responsible for cell surface alteration. Increment or decrement of phosphatidylserine (PS) expression, asialoglycoprotein receptors (ASGPRs) and sugar residue expression on hepatocyte surfaces was measured in parallel with apoptosis and proliferation. When GdCl 3 was injected 24 h before Pb(NO 3 ) 2 injection, liver modifications were significantly reduced, thus suggesting that GdCl 3 could prevent and/or reduce liver damage.