Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jun;81(6):1865–1872. doi: 10.1172/JCI113532

Specific correction of impaired acid hydrolase secretion in storage pool-deficient platelets by adenosine diphosphate.

B Lages 1, C A Dangelmaier 1, H Holmsen 1, H J Weiss 1
PMCID: PMC442637  PMID: 2968367

Abstract

Storage pool-deficient (SPD) platelets, which have decreased amounts of dense-granule and/or alpha-granule constituents, contain normal amounts of lysosomal acid hydrolases, but in some cases exhibit impaired secretion of these enzymes. We examined this impaired secretion response in SPD patients with varying extents of granule deficiencies, and determined the effects of added dense-granule constituents. Acid hydrolase secretion was impaired in patients with severe dense-granule deficiencies, but not in patients with lesser dense-granule deficiencies, including those with alpha-granule deficiencies as well. When dense-granule constituents (ADP, ATP, serotonin, Ca+2, pyrophosphate) were added to gel-filtered platelets, ADP, but none of the other constituents, completely corrected the impairment of thrombin and A23187-induced secretion in SPD platelets. The concentration of ADP required to normalize thrombin-induced secretion varied markedly, from 0.01 to 10 microM, among the individual patients. Fixation of platelets with formaldehyde before centrifugation did not prevent the enhancement of secretion by ADP. Excess ATP, which acts as a specific antagonist of ADP-mediated responses, completely blocked this enhancement of secretion in SPD platelets by ADP, and partially inhibited acid hydrolase secretion induced by low, but not high, concentrations of thrombin in normal platelets as well. Treatment of normal platelets with acetylsalicylic acid in vivo, but not in vitro, produced an impairment of acid hydrolase secretion similar in extent to that in SPD platelets, but which could not be completely corrected by added ADP. One possible explanation of these results is that the impairment of acid hydrolase secretion may be secondary to the dense-granule deficiency in SPD platelets, and that secreted ADP may potentiate the lysosomal secretion response in normal platelets as well.

Full text

PDF
1865

Images in this article

1867Image
on p.1867

Selected References

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

  1. Bell T. G., Meyers K. M., Prieur D. J., Fauci A. S., Wolff S. M., Padgett G. A. Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets. Blood. 1976 Aug;48(2):175–184. [PubMed] [Google Scholar]
  2. Boxer G. J., Holmsen H., Robkin L., Bang N. U., Boxer L. A., Baehner R. L. Abnormal platelet function in Chediak-Higashi syndrome. Br J Haematol. 1977 Apr;35(4):521–533. doi: 10.1111/j.1365-2141.1977.tb00618.x. [DOI] [PubMed] [Google Scholar]
  3. Buchanan M. R., Rischke J. A., Hirsh J. Aspirin inhibits platelet function independent of the acetylation of cyclo-oxygenase. Thromb Res. 1982 Mar 1;25(5):363–373. doi: 10.1016/0049-3848(82)90127-x. [DOI] [PubMed] [Google Scholar]
  4. Da Prada M., Picotti G. B. Content and subcellular localization of catecholamines and 5-hydroxytryptamine in human and animal blood platelets: monoamine distribution between platelets and plasma. Br J Pharmacol. 1979 Apr;65(4):653–662. doi: 10.1111/j.1476-5381.1979.tb07878.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dangelmaier C. A., Holmsen H. Determination of acid hydrolases in human platelets. Anal Biochem. 1980 May 1;104(1):182–191. doi: 10.1016/0003-2697(80)90296-1. [DOI] [PubMed] [Google Scholar]
  6. Day H. J., Holmsen H. Concepts of the blood platelet release reaction. Ser Haematol. 1971;4(1):3–27. [PubMed] [Google Scholar]
  7. Gerrard J. M., Phillips D. R., Rao G. H., Plow E. F., Walz D. A., Ross R., Harker L. A., White J. G. Biochemical studies of two patients with the gray platelet syndrome. Selective deficiency of platelet alpha granules. J Clin Invest. 1980 Jul;66(1):102–109. doi: 10.1172/JCI109823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grant J. A., Scrutton M. C. Positive interaction between agonists in the aggregation response of human blood platelets: interation between ADP, adrenaline and vasopressin. Br J Haematol. 1980 Jan;44(1):109–125. doi: 10.1111/j.1365-2141.1980.tb01189.x. [DOI] [PubMed] [Google Scholar]
  9. Holmsen H., Dangelmaier C. A., Rongved S. Tight coupling of thrombin-induced acid hydrolase secretion and phosphatidate synthesis to receptor occupancy in human platelets. Biochem J. 1984 Aug 15;222(1):157–167. doi: 10.1042/bj2220157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holmsen H., Kaplan K. L., Dangelmaier C. A. Differential energy requirements for platelet responses. A simultaneous study of aggregation, three secretory processes, arachidonate liberation, phosphatidylinositol breakdown and phosphatidate production. Biochem J. 1982 Oct 15;208(1):9–18. doi: 10.1042/bj2080009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Holmsen H., Setkowsky Dangelmaier C. A. Adenine nucleotide metabolism of blood platelets. X. Formaldehyde stops centrifugation-induced secretion after A23187-stimulation and causes breakdown of metabolic ATP. Biochim Biophys Acta. 1977 Mar 29;497(1):46–61. doi: 10.1016/0304-4165(77)90138-6. [DOI] [PubMed] [Google Scholar]
  12. Holmsen H., Setkowsky C. A., Lages B., Day H. J., Weiss H. J., Scrutton M. C. Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease. Blood. 1975 Jul;46(1):131–142. [PubMed] [Google Scholar]
  13. Holmsen H., Weiss H. J. Further evidence for a deficient storage pool of adenine nucleotides in platelets from some patients with thrombocytopathia--"storage pool disease". Blood. 1972 Feb;39(2):197–209. [PubMed] [Google Scholar]
  14. Holmsen H., Weiss H. J. Secretable storage pools in platelets. Annu Rev Med. 1979;30:119–134. doi: 10.1146/annurev.me.30.020179.001003. [DOI] [PubMed] [Google Scholar]
  15. Huang E. M., Detwiler T. C. Characteristics of the synergistic actions of platelet agonists. Blood. 1981 Apr;57(4):685–691. [PubMed] [Google Scholar]
  16. Kinlough-Rathbone R. L., Packham M. A., Reimers H. J., Cazenave J. P., Mustard J. F. Mechanisms of platelet shape change, aggregation, and release induced by collagen, thrombin, or A23,187. J Lab Clin Med. 1977 Oct;90(4):707–719. [PubMed] [Google Scholar]
  17. Koike K., Rao A. K., Holmsen H., Mueller P. S. Platelet secretion defect in patients with the attention deficit disorder and easy bruising. Blood. 1984 Feb;63(2):427–433. [PubMed] [Google Scholar]
  18. Lages B., Holmsen H., Weiss H. J., Dangelmaier C. Thrombin and ionophore A23187-induced dense granule secretion in storage pool deficient platelets: evidence for impaired nucleotide storage as the primary dense granule defect. Blood. 1983 Jan;61(1):154–162. [PubMed] [Google Scholar]
  19. Lages B., Scrutton M. C., Holmsen H. Studies on gel-filtered human platelets: isolation and characterization in a medium containing no added Ca2+, Mg2+, or K+. J Lab Clin Med. 1975 May;85(5):811–825. [PubMed] [Google Scholar]
  20. Lages B., Weiss H. J. Biphasic aggregation responses to ADP and epinephrine in some storage pool deficient platelets: relationship to the role of endogenous ADP in platelet aggregation and secretion. Thromb Haemost. 1980 Jun 18;43(2):147–153. [PubMed] [Google Scholar]
  21. Macfarlane D. E., Mills D. C. The effects of ATP on platelets: evidence against the central role of released ADP in primary aggregation. Blood. 1975 Sep;46(3):309–320. [PubMed] [Google Scholar]
  22. Massini P., Lüscher E. F. The induction of the release reaction in human blood platelets by close cell contact. Thromb Diath Haemorrh. 1971;25(1):13–20. [PubMed] [Google Scholar]
  23. Mills D. C., Robb I. A., Roberts G. C. The release of nucleotides, 5-hydroxytryptamine and enzymes from human blood platelets during aggregation. J Physiol. 1968 Apr;195(3):715–729. doi: 10.1113/jphysiol.1968.sp008484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Packham M. A., Guccione M. A., Chang P. L., Mustard J. F. Platelet aggregation and release: effects of low concentrations of thrombin or collagen. Am J Physiol. 1973 Jul;225(1):38–47. doi: 10.1152/ajplegacy.1973.225.1.38. [DOI] [PubMed] [Google Scholar]
  25. Rao G. H., Gerrard J. M., Witkop C. J., White J. G. Platelet aggregation independent of ADP release or prostaglandin synthesis in patients with hermansky-Pudlak syndrome. Prostaglandins Med. 1981 Apr;6(4):459–472. doi: 10.1016/0161-4630(81)90079-3. [DOI] [PubMed] [Google Scholar]
  26. Rendu F., Breton-Gorius J., Lebret M., Klebanoff C., Buriot D., Griscelli C., Levy-Toledano S., Caen J. P. Evidence that abnormal platelet functions in human Chédiak-Higashi syndrome are the result of a lack of dense bodies. Am J Pathol. 1983 Jun;111(3):307–314. [PMC free article] [PubMed] [Google Scholar]
  27. Rittenhouse S. E. Activation of human platelet phospholipase C by ionophore A23187 is totally dependent upon cyclo-oxygenase products and ADP. Biochem J. 1984 Aug 15;222(1):103–110. doi: 10.1042/bj2220103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Steen V. M., Holmsen H. Synergism between thrombin and epinephrine in human platelets: different dose-response relationships for aggregation and dense granule secretion. Thromb Haemost. 1985 Oct 30;54(3):680–683. [PubMed] [Google Scholar]
  29. Verhoeven A. J., Mommersteeg M. E., Akkerman J. W. Quantification of energy consumption in platelets during thrombin-induced aggregation and secretion. Tight coupling between platelet responses and the increment in energy consumption. Biochem J. 1984 Aug 1;221(3):777–787. doi: 10.1042/bj2210777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Weiss H. J., Chervenick P. A., Zalusky R., Factor A. A familialdefect in platelet function associated with imapired release of adenosine diphosphate. N Engl J Med. 1969 Dec 4;281(23):1264–1270. doi: 10.1056/NEJM196912042812303. [DOI] [PubMed] [Google Scholar]
  31. Weiss H. J. Platelet aggregation, adhesion and adenosine diphosphate release in thrombopathia (platelet factor 3 deficiency). A comparison with Glanzmann's thrombasthenia and von Willebrand's disease. Am J Med. 1967 Oct;43(4):570–578. doi: 10.1016/0002-9343(67)90180-5. [DOI] [PubMed] [Google Scholar]
  32. Weiss H. J., Witte L. D., Kaplan K. L., Lages B. A., Chernoff A., Nossel H. L., Goodman D. S., Baumgartner H. R. Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in alpha-granules, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor. Blood. 1979 Dec;54(6):1296–1319. [PubMed] [Google Scholar]
  33. White J. G. Platelet granule disorders. Crit Rev Oncol Hematol. 1986;4(4):337–377. doi: 10.1016/s1040-8428(86)80027-0. [DOI] [PubMed] [Google Scholar]
  34. Wiley J. S., Kuchibhotla J., Shaller C. C., Colman R. W. Potassium uptake and release by human blood platelets. Blood. 1976 Aug;48(2):185–197. [PubMed] [Google Scholar]
  35. Witte L. D., Kaplan K. L., Nossel H. L., Lages B. A., Weiss H. J., Goodman D. S. Studies of the release from human platelets of the growth factor for cultured human arterial smooth muscle cells. Circ Res. 1978 Mar;42(3):402–409. doi: 10.1161/01.res.42.3.402. [DOI] [PubMed] [Google Scholar]

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

RESOURCES