Inhibition of PMA-induced CD14 Shedding after Clopidogrel

Background: CD14 is a membrane-bound protein predominantly expressed on monocytes. It forms the receptor for bacterial lipopolysaccharide (LPS) along with proteins MD-2 and TLR-4. Shedding of membrane (m)CD14 occurs via a sheddase-mediated process, producing soluble (s)CD14 that has pro- and anti-inflammatory functions. Clopidogrel is a pro-drug requiring biotransformation to an active metabolite. This metabolite contains a thiol group that forms a disulfide bridge with a cysteine residue of the ADP P2Y12 receptor, leading to irreversible inhibition of the receptor. It is known that CD14 shedding from monocytes increases with PMA stimulation, but the effect of clopidogrel on this function is unknown.