Essential requirement of cytosolic phospholipase A2 for activation of the H+ channel in phagocyte-like cells

Alexander Lowenthal, Rachel Levy

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53 Scopus citations


The NADPH oxidase-producing superoxide is the major mechanism by which phagocytes kill invading pathogens. We previously established a model of cytosolic phospholipase A2 (cPLA2)-deficient differentiated PLB985 cells (PLB-D cells) and demonstrated that cPLA2-generated arachidonic acid (AA) is essential for NADPH oxidase activation (Dana, R., Leto, T., Malech, H., and Levy, R. (1998) J. Biol. Chem. 273, 441-445). In the present study, we used this model to determine the physiological role of cPLA2 in the regulation of both the H+ channel and the Na+/H+ antiporter and to study whether NADPH oxidase activation is regulated by either of these transporters. PLB-D cells and two controls: parent PLB-985 cells and PLB-985 cells transfected with the vector only (PLB cells) were differentiated using 1.25% Me2SO or 5 x 10-8 M 1,25-dihydroxyvitamin D3. Activation of differentiated PLB cells resulted in a Zn2+sensitive alkalization, indicating H+ channel activity. In contrast, differentiated PLB-D cells failed to activate the H+ channel, but the addition of exogenous AA fully restored this activity, indicating the role of cPLA2 in H+ channel activation. The presence of the H+ channel inhibitor Zn2+ caused significant inhibition of NADPH oxidase activity, suggesting a role of the H+ channel in regulating oxidase activity. Na+/H+ antiporter activity was stimulated in differentiated PLB-D cells, indicating that cPLA2 does not participate in the regulation of this antiporter. These results establish an essential and specific physiological requirement of cPLA2-generated AA for activation of the H+ channel and suggest the participation of this channel in the regulation of NADPH oxidase activity.

Original languageEnglish
Pages (from-to)21603-21608
Number of pages6
JournalJournal of Biological Chemistry
Issue number31
StatePublished - 30 Jul 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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