Down-modulation through protein kinase C-alpha of lipopolysaccharide-induced expression of membrane CD14 in mouse bone marrow granulocytes.

We have previously shown that stimulation of mouse bone marrow granulocytes (BMC) by lipopolysaccharide (LPS) induces the expression of CD14. We found here that phorbol 12-myristate 13-acetate (PMA) blocks this LPS effect. The aim of this study was to investigate the mechanism by which PMA can block the LPS signaling pathway in BMC. The unmodified binding of a radiolabeled LPS in PMA-treated cells indicated that the PMA effect was not the consequence of a shedding or an internalization of the LPS receptor, but was rather due to a biochemical event that follows the interaction of LPS with its receptor. The observations that a selective activator of protein kinase C (PKC)-alpha (sapintoxin D) mimics the PMA effect, whereas a selective PKC-alpha inhibitor (Ro-320432) antagonizes this effect, suggest a regulatory role of PKC-alpha in the LPS signaling pathway in mouse BMC.