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Human macrophages secret platelet-activating factor acetylhydrolase
D M Stafforini1, M R Elstad, T M McIntyre
1Nora Ecctes Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112.
The Journal of Biological Chemistry
|June 15, 1990
Summary
Macrophages secrete platelet-activating factor acetylhydrolase (PAF-AH), an enzyme that inactivates inflammatory lipids. This finding suggests macrophages limit inflammation by releasing PAF-AH into plasma during monocyte maturation.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Monocyte maturation to macrophages significantly reduces pro-inflammatory lipid platelet-activating factor (PAF) accumulation.
- This decrease correlates with a substantial increase in intracellular PAF acetylhydrolase (PAF-AH) activity.
Purpose of the Study:
- To investigate whether macrophages secrete PAF-AH.
- To characterize the secreted PAF-AH and compare it to plasma PAF-AH.
Main Methods:
- Biochemical assays to compare enzyme activity and inhibitor sensitivity.
- Electrophoretic analysis to assess mobility.
- Lipoprotein association and transfer studies.
- Hydrolysis assays for phospholipids and PAF.
Main Results:
- Macrophages secrete PAF-AH, which is biochemically and immunologically identical to human plasma PAF-AH.
- The secreted enzyme shares sensitivity to inhibitors, electrophoretic mobility, and lipoprotein association characteristics with plasma PAF-AH.
- Both intracellular and secreted PAF-AH hydrolyze oxidatively fragmented phospholipids and PAF.
Conclusions:
- Macrophages are a significant cellular source of plasma PAF-AH.
- Macrophage-secreted PAF-AH plays a role in inactivating lipid mediators in plasma and at inflammatory sites.
- These secretory changes during monocyte-macrophage differentiation may help regulate acute inflammatory responses.