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. 1991 May 2;113(4):743–756. doi: 10.1083/jcb.113.4.743

A novel intracellular compartment with unusual secretory properties in human neutrophils

PMCID: PMC2288977  PMID: 2026647

Abstract

Human neutrophils contain a novel intracellular compartment that is distinct from the previously characterized azurophil and specific granules. This compartment is distinguished by the presence of cytochemically detectable alkaline phosphatase activity. The alkaline phosphatase-containing compartments are short rod-shaped organelles that rapidly undergo a dramatic reorganization upon cell stimulation with either a chemoattractant or an active phorbol ester. Biochemical analysis shows that in unstimulated neutrophils the majority of the alkaline phosphatase activity is intracellular, but after stimulation essentially all of this activity becomes associated with the cell surface. The exocytotic pathway is unusual in that these small organelles fuse to form elongated tubular structures before their association with the plasmalemma.

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Selected References

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  1. Badwey J. A., Robinson J. M. Biochemical and cytochemical studies on enzymes that dephosphorylate inositol (1,4,5)-trisphosphate in neutrophils. J Histochem Cytochem. 1991 Mar;39(3):321–329. doi: 10.1177/39.3.1847159. [DOI] [PubMed] [Google Scholar]
  2. Bainton D. F., Farquhar M. G. Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. II. Cytochemistry and electron microscopy of bone marrow cells. J Cell Biol. 1968 Nov;39(2):299–317. doi: 10.1083/jcb.39.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bainton D. F., Miller L. J., Kishimoto T. K., Springer T. A. Leukocyte adhesion receptors are stored in peroxidase-negative granules of human neutrophils. J Exp Med. 1987 Dec 1;166(6):1641–1653. doi: 10.1084/jem.166.6.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bainton D. F., Ullyot J. L., Farquhar M. G. The development of neutrophilic polymorphonuclear leukocytes in human bone marrow. J Exp Med. 1971 Oct 1;134(4):907–934. doi: 10.1084/jem.134.4.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berger M., Medof M. E. Increased expression of complement decay-accelerating factor during activation of human neutrophils. J Clin Invest. 1987 Jan;79(1):214–220. doi: 10.1172/JCI112786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borregaard N., Heiple J. M., Simons E. R., Clark R. A. Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. J Cell Biol. 1983 Jul;97(1):52–61. doi: 10.1083/jcb.97.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Borregaard N., Miller L. J., Springer T. A. Chemoattractant-regulated mobilization of a novel intracellular compartment in human neutrophils. Science. 1987 Sep 4;237(4819):1204–1206. doi: 10.1126/science.3629236. [DOI] [PubMed] [Google Scholar]
  8. Borregaard N. The human neutrophil. Function and dysfunction. Eur J Haematol. 1988 Nov;41(5):401–413. doi: 10.1111/j.1600-0609.1988.tb00219.x. [DOI] [PubMed] [Google Scholar]
  9. Brederoo P., van der Meulen J., Mommaas-Kienhuis A. M. Development of the granule population in neutrophil granulocytes from human bone marrow. Cell Tissue Res. 1983;234(3):469–496. doi: 10.1007/BF00218646. [DOI] [PubMed] [Google Scholar]
  10. Burroughs S. F., Devine D. V., Browne G., Kaplan M. E. The population of paroxysmal nocturnal hemoglobinuria neutrophils deficient in decay-accelerating factor is also deficient in alkaline phosphatase. Blood. 1988 Apr;71(4):1086–1089. [PubMed] [Google Scholar]
  11. Curnutte J. T., Babior B. M. Chronic granulomatous disease. Adv Hum Genet. 1987;16:229–297. doi: 10.1007/978-1-4757-0620-8_4. [DOI] [PubMed] [Google Scholar]
  12. Cyboron G. W., Wuthier R. E. Purification and initial characterization of intrinsic membrane-bound alkaline phosphatase from chicken epiphyseal cartilage. J Biol Chem. 1981 Jul 25;256(14):7262–7268. [PubMed] [Google Scholar]
  13. DePierre J. W., Karnovsky M. L. Ecto-enzymes of the guinea pig polymorphonuclear leukocyte. I. Evidence for an ecto-adenosine monophosphatase, adenosine triphosphatase, and -p-nitrophenyl phosphates. J Biol Chem. 1974 Nov 25;249(22):7111–7120. [PubMed] [Google Scholar]
  14. Dewald B., Bretz U., Baggiolini M. Release of gelatinase from a novel secretory compartment of human neutrophils. J Clin Invest. 1982 Sep;70(3):518–525. doi: 10.1172/JCI110643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ganz T., Selsted M. E., Szklarek D., Harwig S. S., Daher K., Bainton D. F., Lehrer R. I. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. doi: 10.1172/JCI112120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Griffiths G., McDowall A., Back R., Dubochet J. On the preparation of cryosections for immunocytochemistry. J Ultrastruct Res. 1984 Oct;89(1):65–78. doi: 10.1016/s0022-5320(84)80024-6. [DOI] [PubMed] [Google Scholar]
  17. Heuser J. Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. J Cell Biol. 1989 Mar;108(3):855–864. doi: 10.1083/jcb.108.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Huizinga T. W., van der Schoot C. E., Jost C., Klaassen R., Kleijer M., von dem Borne A. E., Roos D., Tetteroo P. A. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Nature. 1988 Jun 16;333(6174):667–669. doi: 10.1038/333667a0. [DOI] [PubMed] [Google Scholar]
  19. Jesaitis A. J., Buescher E. S., Harrison D., Quinn M. T., Parkos C. A., Livesey S., Linner J. Ultrastructural localization of cytochrome b in the membranes of resting and phagocytosing human granulocytes. J Clin Invest. 1990 Mar;85(3):821–835. doi: 10.1172/JCI114509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jost C. R., Huizinga T. W., de Goede R., Fransen J. A., Tetteroo P. A., Daha M. R., Ginsel L. A. Intracellular localization and de novo synthesis of FcRIII in human neutrophil granulocytes. Blood. 1990 Jan 1;75(1):144–151. [PubMed] [Google Scholar]
  21. Krause K. H., Lew P. D. Subcellular distribution of Ca2+ pumping sites in human neutrophils. J Clin Invest. 1987 Jul;80(1):107–116. doi: 10.1172/JCI113035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Low M. G. Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J. 1987 May 15;244(1):1–13. doi: 10.1042/bj2440001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Modrzakowski M. C., Spitznagel J. K. Bactericidal activity of fractionated granule contents from human polymorphonuclear leukocytes: antagonism of granule cationic proteins by lipopolysaccharide. Infect Immun. 1979 Aug;25(2):597–602. doi: 10.1128/iai.25.2.597-602.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  25. O'Flaherty J. T., Redman J. F., Jacobson D. P. Cyclical binding, processing, and functional interactions of neutrophils with leukotriene B4. J Cell Physiol. 1990 Feb;142(2):299–308. doi: 10.1002/jcp.1041420212. [DOI] [PubMed] [Google Scholar]
  26. Ohno Y., Seligmann B. E., Gallin J. I. Cytochrome b translocation to human neutrophil plasma membranes and superoxide release. Differential effects of N-formylmethionylleucylphenylalanine, phorbol myristate acetate, and A23187. J Biol Chem. 1985 Feb 25;260(4):2409–2414. [PubMed] [Google Scholar]
  27. Parkos C. A., Cochrane C. G., Schmitt M., Jesaitis A. J. Regulation of the oxidative response of human granulocytes to chemoattractants. No evidence for stimulated traffic of redox enzymes between endo and plasma membranes. J Biol Chem. 1985 Jun 10;260(11):6541–6547. [PubMed] [Google Scholar]
  28. Robinson J. M., Badwey J. A., Karnovsky M. L., Karnovsky M. J. Cell surface dynamics of neutrophils stimulated with phorbol esters or retinoids. J Cell Biol. 1987 Jul;105(1):417–426. doi: 10.1083/jcb.105.1.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Robinson J. M. Improved localization of intracellular sites of phosphatases using cerium and cell permeabilization. J Histochem Cytochem. 1985 Aug;33(8):749–754. doi: 10.1177/33.8.2991362. [DOI] [PubMed] [Google Scholar]
  30. Robinson J. M., Karnovsky M. J. Ultrastructural localization of several phosphatases with cerium. J Histochem Cytochem. 1983 Oct;31(10):1197–1208. doi: 10.1177/31.10.6309949. [DOI] [PubMed] [Google Scholar]
  31. Robinson J. M., Karnovsky M. L., Karnovsky M. J. Glycogen accumulation in polymorphonuclear leukocytes, and other intracellular alterations that occur during inflammation. J Cell Biol. 1982 Dec;95(3):933–942. doi: 10.1083/jcb.95.3.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Robinson J. M., Okada T., Castellot J. J., Jr, Karnovsky M. J. Unusual lysosomes in aortic smooth muscle cells: presence in living and rapidly frozen cells. J Cell Biol. 1986 May;102(5):1615–1622. doi: 10.1083/jcb.102.5.1615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rothberg K. G., Ying Y. S., Kamen B. A., Anderson R. G. Cholesterol controls the clustering of the glycophospholipid-anchored membrane receptor for 5-methyltetrahydrofolate. J Cell Biol. 1990 Dec;111(6 Pt 2):2931–2938. doi: 10.1083/jcb.111.6.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rothberg K. G., Ying Y. S., Kolhouse J. F., Kamen B. A., Anderson R. G. The glycophospholipid-linked folate receptor internalizes folate without entering the clathrin-coated pit endocytic pathway. J Cell Biol. 1990 Mar;110(3):637–649. doi: 10.1083/jcb.110.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Selvaraj P., Rosse W. F., Silber R., Springer T. A. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature. 1988 Jun 9;333(6173):565–567. doi: 10.1038/333565a0. [DOI] [PubMed] [Google Scholar]
  36. Singer I. I., Scott S., Kawka D. W., Kazazis D. M. Adhesomes: specific granules containing receptors for laminin, C3bi/fibrinogen, fibronectin, and vitronectin in human polymorphonuclear leukocytes and monocytes. J Cell Biol. 1989 Dec;109(6 Pt 1):3169–3182. doi: 10.1083/jcb.109.6.3169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Spicer S. S., Hardin J. H. Ultrastructure, cytochemistry, and function of neutrophil leukocyte granules. A review. Lab Invest. 1969 May;20(5):488–497. [PubMed] [Google Scholar]
  38. Todd R. F., 3rd, Arnaout M. A., Rosin R. E., Crowley C. A., Peters W. A., Babior B. M. Subcellular localization of the large subunit of Mo1 (Mo1 alpha; formerly gp 110), a surface glycoprotein associated with neutrophil adhesion. J Clin Invest. 1984 Oct;74(4):1280–1290. doi: 10.1172/JCI111538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tokuyasu K. T. Immunochemistry on ultrathin frozen sections. Histochem J. 1980 Jul;12(4):381–403. doi: 10.1007/BF01011956. [DOI] [PubMed] [Google Scholar]
  40. Weiss J., Elsbach P., Olsson I., Odeberg H. Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem. 1978 Apr 25;253(8):2664–2672. [PubMed] [Google Scholar]
  41. Weiss S. J., Klein R., Slivka A., Wei M. Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. J Clin Invest. 1982 Sep;70(3):598–607. doi: 10.1172/JCI110652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wilson P. D., Smith G. P., Peters T. J. Pyridoxal 5'-phosphate: a possible physiological substrate for alkaline phosphatase in human neutrophils. Histochem J. 1983 Mar;15(3):257–264. doi: 10.1007/BF01006240. [DOI] [PubMed] [Google Scholar]
  43. Yoon P. S., Boxer L. A., Mayo L. A., Yang A. Y., Wicha M. S. Human neutrophil laminin receptors: activation-dependent receptor expression. J Immunol. 1987 Jan 1;138(1):259–265. [PubMed] [Google Scholar]

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