DIFFERENTIAL-EFFECTS OF CELL ADHERENCE ON LPS-STIMULATED CYTOKINE PRODUCTION BY HUMAN MONOCYTES AND MACROPHAGES

It is well known that adherence of monocytes (MO) to extracellular mat rix substrates or tissue culture plastic activates these cells and ind uces the expression of a multitude of genes. Especially, it was descri bed, that MO are primed by cell adhesion to produce higher amounts of some cytokines, e.g. interleukin (IL)-8 and tumor necrosis factor alph a (TNF-alpha). In order to investigate adherence-induced effects upon cytokine production, we seeded MO into tissue cultures and stimulated cells by lipopolysaccharide (LPS) simultaneously or at later time poin ts. An increasing time-lag between cell adhesion and LPS-stimulation l ed to differential effects upon cytokine production: whereas TNF was u pregulated (in accordance with reports by others), granulocyte colony stimulating factor (G-CSF) was considerably down-regulated. In contras t, G-CSF production did not change, when cells were kept under non-adh erent conditions in n hole blood. In adherent cultures down-regulation of G-CSF could already be observed after two hours with a maximum aft er 24 h and was paralleled by a much lower abundance of G-CSF mRNA. Ad hesion induced a significant suppression of G-CSF comparable to MO, if mature macrophages derived from MO in vitro were examined. Furthermor e, two other cytokines, granulocyte-macrophage (GM)-CSF and IL-6, were also down-regulated following adhesion. In conclusion, activation of mononuclear phagocytes by adhesion can Lead to ''priming'' for the ''s ilencing'' for the production of others.