Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞
Stimulated inflammatory cells synthesize platelet-activating factor (PAF), but lysates of these cells show little enhancement in PAF synthase activity. We show that human neutrophils contain intracellular plasma PAF acetylhydrolase (PLA2G7), an enzyme normally secreted by monocytes. The esterase inh...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2007-11-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520424368 |
| _version_ | 1818671441961287680 |
|---|---|
| author | Jiawei Chen Lili Yang Jason M. Foulks Andrew S. Weyrich Gopal K. Marathe Thomas M. McIntyre |
| author_facet | Jiawei Chen Lili Yang Jason M. Foulks Andrew S. Weyrich Gopal K. Marathe Thomas M. McIntyre |
| author_sort | Jiawei Chen |
| collection | DOAJ |
| description | Stimulated inflammatory cells synthesize platelet-activating factor (PAF), but lysates of these cells show little enhancement in PAF synthase activity. We show that human neutrophils contain intracellular plasma PAF acetylhydrolase (PLA2G7), an enzyme normally secreted by monocytes. The esterase inhibitors methyl arachidonoylfluorophosphonate (MAFP), its linoleoyl homolog, and Pefabloc inhibit plasma PAF acetylhydrolase. All of these inhibitors induced PAF accumulation by quiescent neutrophils and monocytes that was equivalent to agonist stimulation. Agonist stimulation after esterase inhibition did not further increase PAF accumulation. PAF acetylhydrolase activity in intact neutrophils was reduced, but not abolished, by agonist stimulation. Erythrocytes, which do not participate in the acute inflammatory response, inexplicably express the type I PAF acetylhydrolase, whose only known substrate is PAF. Inhibition of this enzyme by MAFP caused PAF accumulation by erythrocytes, which was hemolytic in the absence of PAF acetylhydrolase activity. We propose that PAF is continuously synthesized by a nonselective acyltransferase activity(ies) found even in noninflammatory cells as a component of membrane remodeling, which is then selectively and continually degraded by intracellular PAF acetylhydrolase activity to modulate PAF production. |
| first_indexed | 2024-12-17T07:24:04Z |
| format | Article |
| id | doaj.art-c7360768e04b4b9cab4c3d1314dc50aa |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T07:24:04Z |
| publishDate | 2007-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c7360768e04b4b9cab4c3d1314dc50aa2022-12-21T21:58:42ZengElsevierJournal of Lipid Research0022-22752007-11-01481123652376Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞Jiawei Chen0Lili Yang1Jason M. Foulks2Andrew S. Weyrich3Gopal K. Marathe4Thomas M. McIntyre5Department of Cell Biology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195Department of Cell Biology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195Department of Experimental Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112Departments of Internal Medicine and Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112Department of Cell Biology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195Department of Cell Biology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195; Department of Experimental Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112Stimulated inflammatory cells synthesize platelet-activating factor (PAF), but lysates of these cells show little enhancement in PAF synthase activity. We show that human neutrophils contain intracellular plasma PAF acetylhydrolase (PLA2G7), an enzyme normally secreted by monocytes. The esterase inhibitors methyl arachidonoylfluorophosphonate (MAFP), its linoleoyl homolog, and Pefabloc inhibit plasma PAF acetylhydrolase. All of these inhibitors induced PAF accumulation by quiescent neutrophils and monocytes that was equivalent to agonist stimulation. Agonist stimulation after esterase inhibition did not further increase PAF accumulation. PAF acetylhydrolase activity in intact neutrophils was reduced, but not abolished, by agonist stimulation. Erythrocytes, which do not participate in the acute inflammatory response, inexplicably express the type I PAF acetylhydrolase, whose only known substrate is PAF. Inhibition of this enzyme by MAFP caused PAF accumulation by erythrocytes, which was hemolytic in the absence of PAF acetylhydrolase activity. We propose that PAF is continuously synthesized by a nonselective acyltransferase activity(ies) found even in noninflammatory cells as a component of membrane remodeling, which is then selectively and continually degraded by intracellular PAF acetylhydrolase activity to modulate PAF production.http://www.sciencedirect.com/science/article/pii/S0022227520424368platelet-activating factorrecyclingmethyl arachidonoylfluorophosphonatePefablocphospholipaselipoprotein-associated phospholipase A2 |
| spellingShingle | Jiawei Chen Lili Yang Jason M. Foulks Andrew S. Weyrich Gopal K. Marathe Thomas M. McIntyre Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞ Journal of Lipid Research platelet-activating factor recycling methyl arachidonoylfluorophosphonate Pefabloc phospholipase lipoprotein-associated phospholipase A2 |
| title | Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞ |
| title_full | Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞ |
| title_fullStr | Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞ |
| title_full_unstemmed | Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞ |
| title_short | Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesiss⃞ |
| title_sort | intracellular paf catabolism by paf acetylhydrolase counteracts continual paf synthesiss⃞ |
| topic | platelet-activating factor recycling methyl arachidonoylfluorophosphonate Pefabloc phospholipase lipoprotein-associated phospholipase A2 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520424368 |
| work_keys_str_mv | AT jiaweichen intracellularpafcatabolismbypafacetylhydrolasecounteractscontinualpafsynthesiss AT liliyang intracellularpafcatabolismbypafacetylhydrolasecounteractscontinualpafsynthesiss AT jasonmfoulks intracellularpafcatabolismbypafacetylhydrolasecounteractscontinualpafsynthesiss AT andrewsweyrich intracellularpafcatabolismbypafacetylhydrolasecounteractscontinualpafsynthesiss AT gopalkmarathe intracellularpafcatabolismbypafacetylhydrolasecounteractscontinualpafsynthesiss AT thomasmmcintyre intracellularpafcatabolismbypafacetylhydrolasecounteractscontinualpafsynthesiss |