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J. Biol. Chem., Vol. 279, Issue 41, 42605-42611, October 8, 2004

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Lysosomal Phospholipase A2 Is Selectively Expressed in Alveolar Macrophages^*

Akira Abe, Miki Hiraoka, Susan Wild, Steven E. Wilcoxen, Robert Paine, III, and James A. Shayman¶

From the Division of Nephrology and Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109

Lung surfactant is the surface-active agent comprised of phospholipids and proteins that lines pulmonary alveoli. Surfactant stabilizes the alveolar volume by reducing surface tension. Previously, we identified a lysosomal phospholipase A2, termed LPLA2, with specificity toward phosphatidylcholine and phosphatidylethanolamine. The phospholipase is localized to lysosomes, is calcium-independent, has an acidic pH optimum, and transacylates ceramide. Here, we demonstrate that LPLA2 is selectively expressed in alveolar macrophages but not in peritoneal macrophages, peripheral blood monocytes, or other tissues. Other macrophage-associated phospholipase A2s do not show a comparable distribution. LPLA2 is of high specific activity and recognizes disaturated phosphatidylcholine as a substrate. The lysosomal phospholipase A2 activity is six times lower in alveolar macrophages from mice with a targeted deletion of the granulocyte macrophage colony-stimulating factor (GM-CSF), a model of impaired surfactant catabolism, compared with those from wild-type mice. However, LPLA2 activity and protein levels are measured in GM-CSF null mice in which GM-CSF is expressed as a transgene under the control of the surfactant protein C promoter. Thus LPLA2 may be a major enzyme of pulmonary surfactant phospholipid degradation by alveolar macrophages and may be deficient in disorders of surfactant metabolism.

Received for publication, July 12, 2004 , and in revised form, August 4, 2004.

^* This work is supported by grants from the Michigan Economic Development Corporation Life Sciences Corridor Fund (to J. A. S.), National Institutes of Health Grants RO1 DK55823 (to J. A. S.) and HL64558 (to R. P.), and a Veterans Administration Merit Review (to R. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY490816.

^¶ To whom correspondence should be addressed: Nephrology Division, Dept. of Internal Medicine, University of Michigan, Box 0676, Rm. 1560 MSRBII, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0676. Tel.: 734-763-0992; Fax: 734-763-0982; E-mail: jshayman{at}umich.edu.

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