Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Dec;82(6):1983–1991. doi: 10.1172/JCI113818

Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.

M Miwa 1, T Miyake 1, T Yamanaka 1, J Sugatani 1, Y Suzuki 1, S Sakata 1, Y Araki 1, M Matsumoto 1
PMCID: PMC442780  PMID: 3198761

Abstract

Platelet-activating factor (PAF) acetylhydrolase has been recognized as an enzyme that inactivates PAF. We developed a convenient and reproducible method for determining human serum PAF acetylhydrolase activity. The assay was based on measurement of [14C]acetate produced from 1-O-alkyl-2-[14C]-acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of radioactive substrate and albumin with TCA. The apparent Km value of PAF acetylhydrolase (near the physiological concentration of serum protein) was 1.5 X 10(-4) M PAF. 32 subjects with serum PAF acetylhydrolase deficiency were found among 816 healthy Japanese adults. The low PAF acetylhydrolase activity in the deficient serum might not be due to the presence of enzyme inhibitor. Both the sensitivity to PAF and the metabolism of PAF in platelets from PAF acetylhydrolase-deficient subjects were almost the same as those of normal subjects. Deficiency in serum PAF acetylhydrolase appeared to be transmitted by autosomal recessive heredity among five Japanese families. Among healthy adults, healthy children, and asthmatic children, who were grouped into five classes on the basis of respiratory symptoms (remission, wheezy, mild, moderate, and severe groups), the probability of PAF acetylhydrolase deficiency was significantly higher in groups with severe symptoms (moderate and severe) (P less than 0.01). These results suggest that deficiency of serum PAF acetylhydrolase might be one of the factors leading to severe respiratory symptoms in asthmatic children.

Full text

PDF
1983

Images in this article

1987Image
on p.1987

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alam I., Smith J. B., Silver M. J. Metabolism of platelet-activating factor by blood platelets and plasma. Lipids. 1983 Aug;18(8):534–538. doi: 10.1007/BF02535393. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Benveniste J., Tencé M., Varenne P., Bidault J., Boullet C., Polonsky J. Semi-synthèse et structure proposée du facteur activant les plaquettes (P.A.F.): PAF-acether, un alkyl ether analogue de la lysophosphatidylcholine. C R Seances Acad Sci D. 1979 Nov 26;289(14):1037–1040. [PubMed] [Google Scholar]
  4. Blank M. L., Hall M. N., Cress E. A., Snyder F. Inactivation of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine by a plasma acetylhydrolase: higher activities in hypertensive rats. Biochem Biophys Res Commun. 1983 Jun 15;113(2):666–671. doi: 10.1016/0006-291x(83)91778-3. [DOI] [PubMed] [Google Scholar]
  5. Blank M. L., Lee T., Fitzgerald V., Snyder F. A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid). J Biol Chem. 1981 Jan 10;256(1):175–178. [PubMed] [Google Scholar]
  6. Blank M. L., Snyder F., Byers L. W., Brooks B., Muirhead E. E. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1194–1200. doi: 10.1016/0006-291x(79)91163-x. [DOI] [PubMed] [Google Scholar]
  7. Camussi G., Pawlowski I., Bussolino F., Caldwell P. R., Brentjens J., Andres G. Release of platelet activating factor in rabbits with antibody-mediated injury of the lung: the role of leukocytes and of pulmonary endothelial cells. J Immunol. 1983 Oct;131(4):1802–1807. [PubMed] [Google Scholar]
  8. Cazenave J. P., Benveniste J., Mustard J. F. Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs. Lab Invest. 1979 Sep;41(3):275–285. [PubMed] [Google Scholar]
  9. Chilton F. H., Ellis J. M., Olson S. C., Wykle R. L. 1-O-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine. A common source of platelet-activating factor and arachidonate in human polymorphonuclear leukocytes. J Biol Chem. 1984 Oct 10;259(19):12014–12019. [PubMed] [Google Scholar]
  10. Chilton F. H., O'Flaherty J. T., Ellis J. M., Swendsen C. L., Wykle R. L. Metabolic fate of platelet-activating factor in neutrophils. J Biol Chem. 1983 May 25;258(10):6357–6361. [PubMed] [Google Scholar]
  11. Chilton F. H., O'Flaherty J. T., Ellis J. M., Swendsen C. L., Wykle R. L. Selective acylation of lyso platelet activating factor by arachidonate in human neutrophils. J Biol Chem. 1983 Jun 25;258(12):7268–7271. [PubMed] [Google Scholar]
  12. Demopoulos C. A., Pinckard R. N., Hanahan D. J. Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem. 1979 Oct 10;254(19):9355–9358. [PubMed] [Google Scholar]
  13. Doebber T. W., Wu M. S., Robbins J. C., Choy B. M., Chang M. N., Shen T. Y. Platelet activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone. Biochem Biophys Res Commun. 1985 Mar 29;127(3):799–808. doi: 10.1016/s0006-291x(85)80014-0. [DOI] [PubMed] [Google Scholar]
  14. Farr R. S., Cox C. P., Wardlow M. L., Jorgensen R. Preliminary studies of an acid-labile factor (ALF) in human sera that inactivates platelet-activating factor (PAF). Clin Immunol Immunopathol. 1980 Mar;15(3):318–330. doi: 10.1016/0090-1229(80)90044-6. [DOI] [PubMed] [Google Scholar]
  15. Findlay S. R., Lichtenstein L. M., Hanahan D. J., Pinckard R. N. Contraction of guinea pig ileal smooth muscle by acetyl glyceryl ether phosphorylcholine. Am J Physiol. 1981 Sep;241(3):C130–C133. doi: 10.1152/ajpcell.1981.241.3.C130. [DOI] [PubMed] [Google Scholar]
  16. Halonen M., Palmer J. D., Lohman I. C., McManus L. M., Pinckard R. N. Respiratory and circulatory alterations induced by acetyl glyceryl ether phosphorylcholine, a mediator of IgE anaphylaxis in the rabbit. Am Rev Respir Dis. 1980 Dec;122(6):915–924. doi: 10.1164/arrd.1980.122.6.915. [DOI] [PubMed] [Google Scholar]
  17. Hanahan D. J., Demopoulos C. A., Liehr J., Pinckard R. N. Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine. J Biol Chem. 1980 Jun 25;255(12):5514–5516. [PubMed] [Google Scholar]
  18. Heffner J. E., Shoemaker S. A., Canham E. M., Patel M., McMurtry I. F., Morris H. G., Repine J. E. Acetyl glyceryl ether phosphorylcholine-stimulated human platelets cause pulmonary hypertension and edema in isolated rabbit lungs. Role of thromboxane A2. J Clin Invest. 1983 Feb;71(2):351–357. doi: 10.1172/JCI110776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Humphrey D. M., Hanahan D. J., Pinckard R. N. Induction of leukocytic infiltrates in rabbit skin by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1982 Sep;47(3):227–234. [PubMed] [Google Scholar]
  20. Humphrey D. M., McManus L. M., Hanahan D. J., Pinckard R. N. Morphologic basis of increased vascular permeability induced by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1984 Jan;50(1):16–25. [PubMed] [Google Scholar]
  21. Humphrey D. M., McManus L. M., Satouchi K., Hanahan D. J., Pinckard R. N. Vasoactive properties of acetyl glyceryl ether phosphorylcholine and analogues. Lab Invest. 1982 Apr;46(4):422–427. [PubMed] [Google Scholar]
  22. Lapetina E. G. Platelet-activating factor stimulates the phosphatidylinositol cycle. Appearance of phosphatidic acid is associated with the release of serotonin in horse platelets. J Biol Chem. 1982 Jul 10;257(13):7314–7317. [PubMed] [Google Scholar]
  23. Lee T. C., Malone B., Wasserman S. I., Fitzgerald V., Snyder F. Activities of enzymes that metabolize platelet-activating factor (1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine) in neutrophils and eosinophils from humans and the effect of a calcium ionophore. Biochem Biophys Res Commun. 1982 Apr 29;105(4):1303–1308. doi: 10.1016/0006-291x(82)90928-7. [DOI] [PubMed] [Google Scholar]
  24. Lynch J. M., Lotner G. Z., Betz S. J., Henson P. M. The release of a platelet-activating factor by stimulated rabbit neutrophils. J Immunol. 1979 Sep;123(3):1219–1226. [PubMed] [Google Scholar]
  25. MUIRHEAD E. E., STIRMAN J. A., JONES F. Renal autoexplantation and protection against renoprival hypertensive cardiovascular disease and hemolysis. J Clin Invest. 1960 Feb;39:266–281. doi: 10.1172/JCI104037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Malone B., Lee T., Snyder F. Inactivation of platelet activating factor by rabbit platelets. Lyso-platelet activating factor as a key intermediate with phosphatidylcholine as the source of arachidonic acid in its conversion to a tetraenoic acylated product. J Biol Chem. 1985 Feb 10;260(3):1531–1534. [PubMed] [Google Scholar]
  27. Marcus A. J., Safier L. B., Ullman H. L., Wong K. T., Broekman M. J., Weksler B. B., Kaplan K. L. Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro. Blood. 1981 Nov;58(5):1027–1031. [PubMed] [Google Scholar]
  28. McManus L. M., Hanahan D. J., Pinckard R. N. Human platelet stimulation by acetyl glyceryl ether phosphorylcholine. J Clin Invest. 1981 Mar;67(3):903–906. doi: 10.1172/JCI110108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McManus L. M. Pathobiology of platelet-activating factors. Pathol Immunopathol Res. 1986;5(2):104–117. doi: 10.1159/000157006. [DOI] [PubMed] [Google Scholar]
  30. Miwa M., Hill C., Kumar R., Sugatani J., Olson M. S., Hanahan D. J. Occurrence of an endogenous inhibitor of platelet-activating factor in rat liver. J Biol Chem. 1987 Jan 15;262(2):527–530. [PubMed] [Google Scholar]
  31. Miwa M., Matsumoto M., Tezuka M., Okada S., Ohsuka S., Fujiwake H. Quantitative fluorographic detection of 3H and 14C on two-dimensional thin-layer chromatographic sheets by an ultra-high-sensitivity TV camera system. Anal Biochem. 1986 Feb 1;152(2):391–395. doi: 10.1016/0003-2697(86)90425-2. [DOI] [PubMed] [Google Scholar]
  32. Miyake T., Kawamori J., Yoshida T., Hirao T., Osaka F., Matsuki H., Kasuga H. [Analysis of wheezy children in elementary school. Prevalence of wheeze, bronchial asthma, and correlation between serum IgE levels, RAST score to mite and severity of respiratory symptoms]. Arerugi. 1985 Oct;34(10):939–947. [PubMed] [Google Scholar]
  33. Morley J., Page C. P., Mazzoni L., Sanjar S. Effects of ketotifen upon responses to platelet activating factor: a basis for asthma prophylaxis. Ann Allergy. 1986 Apr;56(4):335–340. [PubMed] [Google Scholar]
  34. Nijssen J. G., Roosenboom C. F., van den Bosch H. Identification of a calcium-independent phospholipase A2 in rat lung cytosol and differentiation from acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF-acether). Biochim Biophys Acta. 1986 May 21;876(3):611–618. doi: 10.1016/0005-2760(86)90050-0. [DOI] [PubMed] [Google Scholar]
  35. O'Flaherty J. T., Wykle R. L., Miller C. H., Lewis J. C., Waite M., Bass D. A., McCall C. E., DeChatelet L. R. 1-O-Alkyl-sn-glyceryl-3-phosphorylcholines: a novel class of neutrophil stimulants. Am J Pathol. 1981 Apr;103(1):70–78. [PMC free article] [PubMed] [Google Scholar]
  36. Oda M., Satouchi K., Yasunaga K., Saito K. Polymorphonuclear leukocyte-platelet interactions: acetylglyceryl ether phosphocholine-induced platelet activation under stimulation with chemotactic peptide. J Biochem. 1986 Nov;100(5):1117–1123. doi: 10.1093/oxfordjournals.jbchem.a121815. [DOI] [PubMed] [Google Scholar]
  37. Ostermann G., Rühling K., Zabel-Langhennig R., Winkler L., Schlag B., Till U. Plasma from atherosclerotic patients exerts an increased degradation of platelet-activating factor. Thromb Res. 1987 Aug 1;47(3):279–285. doi: 10.1016/0049-3848(87)90141-1. [DOI] [PubMed] [Google Scholar]
  38. Patterson R., Bernstein P. R., Harris K. E., Krell R. D. Airway responses to sequential challenges with platelet-activating factor and leukotriene D4 in rhesus monkeys. J Lab Clin Med. 1984 Sep;104(3):340–345. [PubMed] [Google Scholar]
  39. Pinckard R. N., Farr R. S., Hanahan D. J. Physicochemical and functional identity of rabbit platelet-activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE sensitized basophils. J Immunol. 1979 Oct;123(4):1847–1857. [PubMed] [Google Scholar]
  40. Pinckard R. N., Farr R. S., Hanahan D. J. Physicochemical and functional identity of rabbit platelet-activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE sensitized basophils. J Immunol. 1979 Oct;123(4):1847–1857. [PubMed] [Google Scholar]
  41. Polonsky J., Tencé M., Varenne P., Das B. C., Lunel J., Benveniste J. Release of 1-O-alkylglyceryl 3-phosphorylcholine, O-deacetyl platelet-activating factor, from leukocytes: chemical ionization mass spectrometry of phospholipids. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7019–7023. doi: 10.1073/pnas.77.12.7019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Stafforini D. M., McIntyre T. M., Carter M. E., Prescott S. M. Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor. J Biol Chem. 1987 Mar 25;262(9):4215–4222. [PubMed] [Google Scholar]
  43. Stafforini D. M., Prescott S. M., McIntyre T. M. Human plasma platelet-activating factor acetylhydrolase. Purification and properties. J Biol Chem. 1987 Mar 25;262(9):4223–4230. [PubMed] [Google Scholar]
  44. Stimler N. P., Bloor C. M., Hugli T. E., Wykle R. L., McCall C. E., O'Flaherty J. T. Anaphylactic actions of platelet-activating factor. Am J Pathol. 1981 Oct;105(1):64–69. [PMC free article] [PubMed] [Google Scholar]
  45. Sugatani J., Miwa M., Hanahan D. J. Platelet-activating factor stimulation of rabbit platelets is blocked by serine protease inhibitor (chymotryptic protease inhibitor). J Biol Chem. 1987 Apr 25;262(12):5740–5747. [PubMed] [Google Scholar]
  46. Tamura N., Agrawal D. K., Suliaman F. A., Townley R. G. Effects of platelet activating factor on the chemotaxis of normodense eosinophils from normal subjects. Biochem Biophys Res Commun. 1987 Feb 13;142(3):638–644. doi: 10.1016/0006-291x(87)91462-8. [DOI] [PubMed] [Google Scholar]
  47. Wardlaw A. J., Moqbel R., Cromwell O., Kay A. B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986 Dec;78(6):1701–1706. doi: 10.1172/JCI112765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Yamashita M., Homma H., Inoue K., Nojima S. The metabolism of platelet activating factor in platelets and plasma of various animals. J Toxicol Sci. 1983 Aug;8(3):177–188. doi: 10.2131/jts.8.177. [DOI] [PubMed] [Google Scholar]
  49. Yanoshita R., Kudo I., Ikizawa K., Chang H. W., Kobayashi S., Ohno M., Nojima S., Inoue K. Hydrolysis of platelet activating factor and its methylated analogs by acetylhydrolases. J Biochem. 1988 May;103(5):815–819. doi: 10.1093/oxfordjournals.jbchem.a122352. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES