title: Presence of the M-type sPLA(2) receptor on neutrophils and its role in elastase release and adhesion.
abstract: Secretory phospholipase A(2) (sPLA(2)) produces lipids that stimulate polymorphonuclear neutrophils (PMNs). With the discovery of sPLA(2) receptors (sPLA(2)-R), we hypothesize that sPLA(2) stimulates PMNs through a receptor. Scatchard analysis was used to determine the presence of a sPLA(2) ligand. Lysates were probed with an antibody to the M-type sPLA(2)-R, and the immunoreactivity was localized. PMNs were treated with active and inactive (+EGTA) sPLA(2) (1-100 units of enzyme activity/ml, types IA, IB, and IIA), and elastase release and PMN adhesion were measured. PMNs incubated with inactive, FITC-linked sPLA(2)-IB, but not sPLA(2)-IA, demonstrated the presence of a sPLA(2)-R with saturation at 2.77 fM and a K(d) of 167 pM. sPLA(2)-R immunoreactivity was present at 185 kDa and localized to the membrane. Inactive sPLA(2)-IB activated p38 MAPK, and p38 MAPK inhibition attenuated elastase release. Active sPLA(2)-IA caused elastase release, but inactive type IA did not. sPLA(2)-IB stimulated elastase release independent of activity; inactive sPLA(2)-IIA partially stimulated PMNs. sPLA(2)-IB and sPLA(2)-IIA caused PMN adhesion. We conclude that PMNs contain a membrane M-type sPLA(2)-R that activates p38 MAPK.
authors.affiliation: Bonfils Blood Center, Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Garret
authors.initials: G
authors.lastname: Zallen
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: David J
authors.initials: DJ
authors.lastname: Elzi
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.forename: Kohji
authors.initials: K
authors.lastname: Hanasaki
authors.forename: Jun
authors.initials: J
authors.lastname: Ishizaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Arita
authors.forename: Lihua
authors.initials: L
authors.lastname: Ao
authors.forename: Kelly M
authors.initials: KM
authors.lastname: England
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D054500:Group IB Phospholipases A2; D054501:Group II Phospholipases A2; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D054507:Receptors, Phospholipase A2; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; C516360:PLA2R1 protein, human; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; D054501:Group II Phospholipases A2; C516202:PLA2G1B protein, human; D019272:Leukocyte Elastase; D002118:Calcium