FUNCTIONAL LIPOPOLYSACCHARIDE RECEPTORS OF LOW-AFFINITY ARE CONSTITUTIVELY EXPRESSED ON MOUSE BONE-MARROW CELLS

Although lipopolysaccharide (LPS)-induced overproduction of cytokines, involved in the pathogenesis of septic shock, occupies the spotlight of endotoxin research, another LPS effect, the differentiation of vari ous cell types including haematopoietic bone marrow cells (BMC), which is probably related to its radioprotective activity, deserves equal a ttention. We have previously established that nanomolar concentrations of LPS trigger in human BMC the expression of CD14 by an induction me chanism independent of CD14 or any other molecule anchored to the cell membrane by a glycosyl phosphatidylinositol glycolipid. We now show t hat this LPS-induced stimulation is triggered by the binding of a smal l number of LPS molecules (13 000 molecules/cell) to constitutive LPS receptors of low affinity (K-d=480 nM). This interaction, which was in hibited by a synthetic LPS antagonist, appeared specific, reversible, saturable, time- and temperature dependent, but was independent of div alent cations, and was inhibited by serum. Exposure of BMC to LPS did not induce a down-modulation of these receptors, but enhanced their se nsitivity to trypsin degradation. Inhibition of LPS binding following different treatments correlated with inhibition of BMC stimulation, th us suggesting that the sparse constitutive receptors of low affinity a re efficient signalling receptors for LPS.