Secretory phospholipase A2 converts the anti-inflammatory high density lipoprotein to a pro-inflammatory particle

S. Kama, F. C. Debeer, A. J. Lusis, M. Navab, A. M. Fogelman

Research output: Contribution to journalArticlepeer-review


Phospholipasc A2 (PLA2) participates in a broad range of cellular processes including coll signaling and is known to be involved in the pathogenesis of inflammatory diseases. Human secretory PLA2 (sPLA2) is secreted by a variety of types in response to the pro-inflammatory cytokines. Vascular smooth muscle cells express high levels of sPLA2 when stimulated with these cytokines. Circulating sPLA2 activity may increase more than 3000-fold during acute phase and extremely high levels have been found in patients with inflammatory arthritis. It has also been suggested that patients with prolonged periods of high plasma sPLA2 activity and seum amyloid A may have high incidence of atherosclerosis. Given the central role of HDL in lipoprotein metabolism and in atherosclerosis, we have investigated the effect of recombinant human sPLA2 on HDL s ability to inhibit LDL oxidation. While sham treated HDL prevented LDL oxidation and monocyte migration by 89±7% in a co-culture model of human artery wall, pretreatment of HDL with sPLA2 followed by reisolation of HDL completely abolished the inhibitory effect of HDL and even amplified the LDL oxidation and the resulting monocyte migration by 93±5%. In addition Hpid hydroperoxide production that was prevented by the sham HDL was markedly increased in the presence of sPLA2 treated HDL (0.15 vs 1.3 nmoi/rnl, respectively, p<0.001). Furthermore, unlike sham treated HDL, enzyme- treated HDL alone (with no LDL present) induced a significant monocvte transmigration in the cocultures. \Ve conclude that treatment with sPLA2 converts HDL to a pro-inflammatory particle.

Original languageEnglish
Pages (from-to)A1274
JournalFASEB Journal
Issue number6
StatePublished - 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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