In vitro 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 E. coli endotoxin (LPS) on human monocytes and peritoneal macrophages (PEC) during in vitro differentiation was studied. Short-term (less than 24 hours) exposure to LPS in concentrations up to 50 microgram/ml did not affect monocyte survival or 51Cr-release, but concentrations of 10 microgram/ml or more reduced monocyte survival when LPS exposure was prolonged to 72 h. Undifferentiated monocytes seemed to be sensitive to this effect. Monocyte and PEC protein synthesis was reduced by nontoxic LPS concentrations in both undifferentiated and differentiated cells. LPS exposure reduced monocyte ingestion and degradation of 125I-labelled Candida albicans, dependent on time and dosage. The induction of monocyte- and PEC-mediated cytoststic activity to tumour cells induced by prolonged in vitro culture was also impaired by LPS. The morphological alterations induced in mononuclear phagocytes by LPS included a changes distribution of cells in the monolayer, changes in membrane structure and apparent reduction of lysosomes. LPS thus interferes adversely with several aspects of human mononuclear phagocyte in vitro differentiation.