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Phospholipase A2, an in vivo immunomodulator
A Bravo Cuellar1, F Homo-Delarche, S Orbach-Arbouys
1Institut de Cancérologie et d'Immunogénétique (Univ. Paris-Sud, Ass. Cl. Bernard & ARC), Hôpital Paul-Brousse, Villejuif, France.
Summary
Injecting phospholipase A2 (PLA2) enhances macrophage phagocytosis and chemiluminescence (CL). This suggests PLA2
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Arachidonic acid (AA) release from membrane phospholipids by phospholipase A2 (PLA2) is crucial for macrophage respiratory burst activation.
- Unsaturated fatty acids, especially AA, are necessary for activating the macrophage respiratory burst.
Purpose of the Study:
- To investigate the effect of in vivo PLA2 injection on macrophage phagocytosis and chemiluminescence (CL).
- To explore how PLA2 influences the respiratory burst in macrophages, particularly in conjunction with immunomodulators and oncostatic drugs.
Main Methods:
- Peritoneal macrophages were harvested 30 minutes after intraperitoneal (i.p.) injection of PLA2.
- Phagocytosis of Candida albicans and chemiluminescence (CL) were measured in response to zymosan stimulation.
- CL sensitivity to inhibitors like potassium cyanide (KCN), catalase, superoxide dismutase (SOD), nordihydroguaiaretic acid (NDGA), and indomethacin was assessed.
- Arachidonic acid (AA) metabolism derivatives (PGE2, 6-keto, PGF1 alpha TXB2, LTC4) were measured to assess cyclooxygenase and lipoxygenase activity.
Main Results:
- PLA2 injection significantly enhanced macrophage phagocytosis of Candida albicans and CL compared to normal cells.
- PLA2 treatment boosted CL in macrophages pre-stimulated with immunomodulators (TDM, bestatin) or oncostatic drugs (ACM).
- CL was insensitive to KCN but inhibited by catalase, SOD, NDGA, and high-dose indomethacin, indicating a role for reactive oxygen species.
- In vivo PLA2 stimulation increased the synthesis of both cyclooxygenase and lipoxygenase AA metabolites.
Conclusions:
- In vivo administration of PLA2 enhances macrophage phagocytic and chemiluminescent responses.
- PLA2-induced stimulation of AA metabolism influences the production of reactive oxygen species, affecting macrophage function.
- The specificity of common inhibitors used in CL studies for AA metabolism is relative and should be interpreted cautiously.