Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase

Raya Dana, Thomas L. Leto, Harry L. Malech, Rachel Levy

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

Arachidonic acid (AA) can trigger activation of the phagocyte NADPH oxidase in a cell-free assay. However, a role for AA in activation of the oxidase in intact cells has not been established, nor has the AA generating enzyme critical to this process been identified. The human myeloid cell line PLB-985 was transfected to express p85 cytosolic phospholipase A2 (cPLA2) antisense mRNA and stable clones were selected that lack detectable cPLA2. cPLA2-deficient PLB-985 cells differentiate similarly to control PLB-985 cells in response to retinoic acid or 1,25-dihydroxyvitamin D3, indicating that cPLA2 is not involved in the differentiation process. Neither cPLA2 nor stimulated [3H]AA release were detectable in differentiated cPLA2- deficient PLB-985 cells, demonstrating that cPLA2 is the major type of PLA2 activated in phagocytic-like cells. Despite the normal synthesis of NADPH oxidase subunits during differentiation of cPLA2-deficient PLB-985 cells, these cells fail to activate NADPH oxidase in response to a variety of soluble and particulate stimuli, but the addition of exogenous AA fully restores oxidase activity. This establishes an essential requirement of cPLA2-generated AA for activation of phagocyte NADPH oxidase.

Original languageEnglish
Pages (from-to)441-445
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number1
DOIs
StatePublished - 2 Jan 1998

Fingerprint

Dive into the research topics of 'Essential requirement of cytosolic phospholipase A<sub>2</sub> for activation of the phagocyte NADPH oxidase'. Together they form a unique fingerprint.

Cite this