CHANGE IN SENSITIVITY TO LIPOPOLYSACCHARIDE DURING THE DIFFERENTIATION OF HUMAN MONOCYTES TO MACROPHAGES IN-VITRO

Mononuclear phagocytes in distinct differentiation stages and cultured under different conditions were tested for their sensitivity towards lipopolysaccharide (LPS), using procoagulant activity (PCA) expression and tumor necrosis factor (TNF) production as indices. The response o f mature monocyte-derived macrophages differed from that of freshly is olated monocytes 1) by higher levels of constititive PCA, 2) by respon ding to approximately 1,000-fold lower concentrations of LPS with PCA and TNF production, and 3) by a faster rise in PCA and TNF production. Due to the high constitutive level of PCA expression, the PCA stimula tion index for LPS was low in macrophages when compared with that in m onocytes. Thus, during differentiation to macrophages, human monocytes acquire increased sensitivity to LPS (2 orders of magnitude more sens itive than a sensitive turbidimetric Limulus amoebocyte lysate assay). This exquisite sensitivity to LPS is expressed regardless of whether LPS is offered in the presence or absence of lipopolysaccharide bindin g protein-containing serum. This points to as yet uncharacterized path ways of high affinity interaction between LPS and macrophages.