Presence of the M-type sPLA2 receptor on neutrophils and its role in elastase release and adhesion

• Published in: American Journal of Physiology: Cell Physiology 2002-10, Vol.283 (4), p.C1102
• Main Authors: Silliman, Christopher C, Moore, Ernest E, Zallen, Garret, Gonzalez, Ricardo, Johnson, Jeffrey L, Elzi, David J, Meng, Xianzhong, Hanasaki, Kohji, Ishizaki, Jun, Arita, Hitoshi, Ao, Lihua, England, Kelly M, Banerjee, Anirban
• Format: Article
• Language: eng ; jpn
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00608.2001

Bonfils Blood Center and Departments of Pediatrics and Surgery, University of Colorado School of Medicine, Denver 80262; Department of Surgery, Denver Health Medical Center, Denver, Colorado 80204; and Shionogi Research Laboratories, Shionogi & Company, Limited, Osaka 541, Japan 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. secretory phospholipase A 2 receptor; p38 mitogen-activated protein kinase