TUMOR PROMOTERS PROTEIN-KINASE-C ACTIVATORS AUGMENT THE SURVIVAL AND FUNCTION OF HUMAN MONOCYTE-DERIVED MACROPHAGES IN LONG-TERM CULTURES

In this study the effect of various Protein kinase C (PKC) activators/ tumour promoters on the maturation and activity of human peripheral bl ood monocytes was examined. Monocytes were cultured in the absence or presence of various PKC activators for up to 2 weeks, and examined for the number of adherent cells, expression of myeloperoxidase enzymes, CD14 antigens, mannose/N-acetylglucosamine (Man/GlcNAc) receptors, and the production of TNF-alpha. The presence of PKC activators in cultur es of monocyte-derived macrophages (HuMoDM) prevented the loss in the number of initially plated monocytes, otherwise observed in long-term tissue cultures with time of incubation. This effect of PKC activators on monocyte survival was diminished in the presence of PKC inhibitors . HuMoDM obtained in the presence of PKC activators maintained a norma l differentiation pattern, as was evident by the loss of granular myel operoxidase enzymes and CD14 antigens, and the acquisition of membrane Man/GlcNAc receptors. HuMoDM which differentiated in the presence of PKC activators also released TNF-alpha in comparable amounts to freshl y harvested human monocytes. PKC activators/tumour promoters augmented the viability of long-term cultures of human monocyte-derived macroph ages. Such macrophages may facilitate cell and molecular biology studi es of differentiated human macrophages.