Lactadherin Inhibits Secretory Phospholipase A(2) Activity on Pre-Apoptotic Leukemia Cells

Secretory phospholipase A(2) (sPLA(2)) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA(2) concentrations are associated with autoimmune diseases and septic shock. Many sPLA(2)’s do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A(2)-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA(2) plateaued at 50–60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA(2) and >70% of human secretory phospholipase A(2)-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA(2).