Presence of the M-type sPLA₂ 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.

Activation of Cytokine Production by Secreted Phospholipase A2 in Human Lung Macrophages Expressing the M-Type Receptor

“…The mRNA for the M-type-R is expressed in human kidney, lung, pancreas, placenta, and skeletal muscle (25,30). Although the presence of the M-type-R has been reported in human neutrophils and monocytes (23,48), the resident cells expressing this receptor in human tissues have not been identified. We provide in this study the first demonstration that the M-type-R is expressed in HLM.…”

“…Finally, some sPLA 2 s interact with specific membrane receptors (21). In particular, it has been suggested that activation of the M-type receptor (M-type-R) may be involved in some in vitro sPLA 2 -induced effects (13,(22)(23)(24). The M-type-R is a 180-kDa protein cloned from various species, including humans (25).…”

Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-κB in Human Neutrophils

“…Recently, it has been suggested that the sPLA 2 receptor is involved in elastase release and neutrophil adhesion (15). Silliman et al (15) demonstrated that human neutrophils express M-type sPLA 2 receptor by using a polyclonal Ab to the human M-type sPLA 2 receptor.…”

“…In our study, we demonstrated that sPLA 2 -IB stimulates CXCL8 production in human neutrophils. On the intracellular signaling pathways induced by sPLA 2 -IB, Silliman et al (15) showed that sPLA 2 -IB stimulated not ERK, but p38 kinase, which performs a crucial role in the elastase release. However, in our study, we found that ERK phosphorylation was dramatically induced by sPLA 2 -IB in human neutrophils, and ERK activity is critically involved in the sPLA 2 -IB-induced CXCL8 production in human neutrophils (Fig.…”

“…CXCL8 (IL-8) is an important cytokine and is released by human neutrophils (12)(13)(14), which have also been reported to express the M-type sPLA 2 receptor (15). Moreover, the stimulation of human neutrophils with sPLA 2 -IB has been reported to cause elastase release and neutrophil adhesion (15).…”