title: Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells.
abstract: Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2'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 A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.
authors.affiliation: Department of Molecular Biology, Aarhus University, Aarhus C, Denmark ; Departments of Medicine, Veterans Administration Boston Healthcare System, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Steffen
authors.initials: S
authors.lastname: Nyegaard
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Novakovic
authors.forename: Jan T
authors.initials: JT
authors.lastname: Rasmussen
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism / Q000494:pharmacology*; D000001:Calcimycin; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D017815:Elapidae / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008894:Milk Proteins / Q000378:metabolism / Q000494:pharmacology*; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D013045:Species Specificity; D013050:Spectrometry, Fluorescence
chemical_list: D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins; D000001:Calcimycin; D054497:Phospholipases A2, Secretory