INVITRO INFLUENCE OF ENDOTOXIN ON HUMAN MONONUCLEAR PHAGOCYTE STRUCTURE AND FUNCTION .1. DEPRESSION OF PROTEIN-SYNTHESIS, PHAGOCYTOSIS OF CANDIDA-ALBICANS AND INDUCTION OF CYTOSTATIC ACTIVITY

Abstract

The effect of Escherichia coli endotoxin (LPS) on human monocytes and peritoneal macrophages (PEC) during in vitro differentiation was studied. Short-term (< 24 h) exposure to LPS in concentrations up to 50 .mu.g/ml did not affect monocyte survival or 51Cr-release; concentrations of 10 .mu.g/ml or more reduced monocyte survival when LPS exposure was prolonged to 72 h. Undifferentiated monocytes seemed more sensitive to this effect. Monocyte and PEC protein synthesis was reduced by non-toxic LPS concentrations in undifferentiated and differentiated cells. LPS exposure reduced monocyte ingestion and degradation of 125I-labeled C. albicans dependent on time and dosage. The induction of monocyte- and PEC-mediated cytostatic activity to tumor [human NHIK 3025] cells induced by prolonged in vitro culture was also impaired by LPS. The morphological alterations induced in mononuclear phagocytes by LPS included a changed distribution of cells in the monolayer, changes in membrane structure and apparent reduction of lysosomes. LPS apparently interferes adversely with several aspects of human mononuclear phagocyte in vitro differentiation.