Human macrophages secret platelet-activating factor acetylhydrolase.
When monocytes mature to macrophages, their ability to accumulate the pro-inflammatory lipid autacoid, platelet-activating factor (PAF), is markedly decreased (Elstad, M. R. Stafforini, D. M., McIntyre, T. M., Prescott, S. M., and Zimmerman, G. A. (1989) J. Biol. Chem. 264, 8467-8470) in conjunction with a 260-fold increase in the activity of intracellular PAF acetylhydrolase (PAF-AH). We now demonstrate that macrophages also secrete PAF-AH and that the secreted enzyme is biochemically and immunologically identical to the human plasma PAF-AH. It is sensitive to the same active-site-directed inhibitors, has the same electrophoretic mobility, is associated with lipoprotein particles, and transfers between low density lipoprotein and high density lipoprotein in a pH-dependent manner like the plasma PAF-AH. In addition, both activities hydrolyze oxidatively fragmented phospholipids and PAF. These data indicate that macrophages are a cellular source of the plasma PAF-AH. Thus, macrophages secrete an enzyme that inactivates lipid mediators at sites of inflammation and in plasma. These changes during the maturation of monocytes to macrophages may serve to limit the acute inflammatory response.
Stafforini
D M
DM
Nora Ecctes Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112.
Elstad
M R
MR
McIntyre
T M
TM
Zimmerman
G A
GA
Prescott
S M
SM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood / Q000302:isolation & purification; D008264:Macrophages / Q000201:enzymology*; D008954:Models, Biological; D010740:Phospholipases / Q000097:blood*; D010741:Phospholipases A / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism
D008074:Lipoproteins; D010740:Phospholipases; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase