Presence of the M-type sPLA 2 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-C1113
• 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: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00608.2001

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.