The Secretion and Uptake of Lysosomal Phospholipase A2 by Alveolar Macrophages

被引:22
|
作者
Abe, Akira [1 ]
Kelly, Robert [1 ]
Kollmeyer, Jessica [1 ]
Hiraoka, Miki [2 ]
Lu, Ye [1 ]
Shayman, James A. [1 ]
机构
[1] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA
[2] Nippon Med Sch, Dept Opthamol, Bunkyo Ku, Tokyo 113, Japan
来源
JOURNAL OF IMMUNOLOGY | 2008年 / 181卷 / 11期
关键词
D O I
10.4049/jimmunol.181.11.7873
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macrophages have long been known to secrete a Phospholipase A(2) with an acidic pH optimum in response to phagocytic stimuli. However, the enzyme or enzymes responsible for this activity have not been identified. We report that mouse alveolar macrophages release lysosomal phospholipase A(2) (LPLA(2)) into the medium of cultured cells following stimulation with zymosan. The release of the enzyme was detected by enzymatic activity assays as well as by Western blotting using an Ab against mouse LPLA(2). LPLA(2) is a high mannose type glycoprotein found in lysosomes, suggesting that the released enzyme might be reincorporated into alveolar macrophages via a mannose or mannose phosphate receptor. Recombinant glycosylated mouse LPLA(2) produced by HEK293 cells was applied to LPLA(2)-deficient (LPLA(2)(-/-)) Mouse alveolar macrophages. The uptake of exogenous LPLA(2) into LPLA(2)(-/-) alveolar macrophages occurred in a concentration-dependent manner. The LPLA(2) taken into the alveolar macrophages colocalized with the lysosomal marker, Lamp-1. This uptake was significantly suppressed in the presence of alpha-methylmannoside but not in the presence of mannose 6-phosphate. Thus, the predominant pathway for uptake of exogenous LPLA(2) is via the mannose receptor, with subsequent translocation into acidic, Lamp-1-associated compartments. LPLA(2)(-/-) alveolar macrophages are characterized by marked accumulation of phosphatidylcholine and phosphatidylethanolamine. Treatment with the recombinant LPLA(2) rescued the LPLA(2)(-/-) alveolar macrophages by markedly decreasing the phospholipid accumulation. The application of a catalytically inactive LPLA(2) revealed that the enzymatic activity of LPLA(2) was required for the phospholipid reduction. These studies identify LPLA(2) as a high m.w.-secreted Phospholipase A(2). The Journal of Immunology, 2008, 181: 7873-7881.
引用
收藏
页码:7873 / 7881
页数:9
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