Am J Physiol Cell Physiol AJP: Heart and Circulatory Physiology
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Am J Physiol Cell Physiol 283: C1102-C1113, 2002. First published May 29, 2002; doi:10.1152/ajpcell.00608.2001
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Vol. 283, Issue 4, C1102-C1113, October 2002

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

Christopher C. Silliman, Ernest E. Moore, Garret Zallen, Ricardo Gonzalez, Jeffrey L. Johnson, David J. Elzi, Xianzhong Meng, Kohji Hanasaki, Jun Ishizaki, Hitoshi Arita, Lihua Ao, Kelly M. England, and Anirban Banerjee

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 A2 (sPLA2) produces lipids that stimulate polymorphonuclear neutrophils (PMNs). With the discovery of sPLA2 receptors (sPLA2-R), we hypothesize that sPLA2 stimulates PMNs through a receptor. Scatchard analysis was used to determine the presence of a sPLA2 ligand. Lysates were probed with an antibody to the M-type sPLA2-R, and the immunoreactivity was localized. PMNs were treated with active and inactive (+EGTA) sPLA2 (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 sPLA2-IB, but not sPLA2-IA, demonstrated the presence of a sPLA2-R with saturation at 2.77 fM and a Kd of 167 pM. sPLA2-R immunoreactivity was present at 185 kDa and localized to the membrane. Inactive sPLA2-IB activated p38 MAPK, and p38 MAPK inhibition attenuated elastase release. Active sPLA2-IA caused elastase release, but inactive type IA did not. sPLA2-IB stimulated elastase release independent of activity; inactive sPLA2-IIA partially stimulated PMNs. sPLA2-IB and sPLA2-IIA caused PMN adhesion. We conclude that PMNs contain a membrane M-type sPLA2-R that activates p38 MAPK.

secretory phospholipase A2 receptor; p38 mitogen-activated protein kinase


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