FIGURE 7.

Model of sPLA₂-IIA function in FLS AA metabolism. Unstimulated cells, AA is mobilized in microparticles esterified to phospholipids. Low level AA release is mediated by cPLA₂-α and is reincorporated into phospholipid pools by acylase(s). AA flux to PGE₂ is very low and is via COX-1. TNF-stimulated cells, TNF. cPLA₂-α is activated (⊕) and COX-2 expression is induced (↑ in circle), stimulating AA flux through the COX-2 pathway to stimulate PGE₂ production. TNF + sPLA₂-IIA, sPLA₂-IIA enzyme activity increases AA mobilization that is not coupled to PGE₂ production. sPLA₂-IIA-mediated signaling superinduces COX-2 (↑↑ in circle) resulting in increased cPLA₂-α-dependent AA flux through COX-2 to PGE₂. sPLA₂-IIA alone increases AA release and induces COX-2 without increasing PGE₂ production. The figure is modeled after Fitzpatrick and Soberman (51).