Phagocytosis of tumor cells by activated liver macrophages.

Abstract

Kupffer cells (KC) are fixed macrophages (Mø) that line the hepatic sinusoids. In response to antigenic or tumor cell challange KC become “activated” and display enhanced biochemical and functional reactivity including increased chemotaxis, phagocytosis, oxidative metabolism and tumor cell killing. We have observed that lipopolysaccharide (LPS)-activated liver Mø phagocytize certain tumor cell targets depending on their tissue origin. This was unusual as Mø typically do not kill tumor targets by phagocytosis. The present studies were designed to study the mechanism involved in liver mø mediated phagocytosis of tumor targets. Mø were isolated from rat livers 48 hr following treatment with LPS (5mg/kg IV) by combined pronase/collagenase perfusion, selective digestion and differential centrifugation. Mø were coincubated on glass coverslips or slides with tumor cells for 48 hr. For both scanning and transmission electron microscopy (SEM,TEM), cells were fixed for 60 min at 4°C in 236 glutaraldehyde buffered by 0.1M cacodylate containing 0.1M sucrose and 1.5mM CaCl 2 (pH 7.4).