Skip to main content

Structure and Function of the Family of Proteoglycans That Reside in the Secretory Granules of Natural Killer Cells and Other Effector Cells of the Immune Response

  • Conference paper
Cytotoxic Effector Mechanisms

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 140))

Abstract

Although it has been known for a number of years that many of the effector cells that participate in immune responses have cell-associated proteoglycans, it has only recently become apparent that these highly acidic macromolecules reside within intracellular secretory granules rather than on the plasma membrane. Heparin proteoglycans are found in the secretory granules of connective tissue mast cells (CTMC) (Benditt et al. 1956; Yurt et al. 1977 a, b; Robinson et al. 1978; Metcalfe et al. 1979, 1980a; Razin et al. 1982; Bland et al. 1982). Chondroitin sulfate proteoglycans are found in the secretory granules of mucosal mast cells (MMC) (Stevens et al. 1986), lung mast cells (Stevens et al. 1988 a), basophils (Orenstein et al. 1978; Rothenberg et al. 1987), eosinophils (Metcalfe et al. 1982), neutrophils (Olsson 1969; Ohhashi et al. 1984), monocytes/ macrophages (Levitt and Ho 1983; Kolset et al. 1984), HL-60 promyelocytic cells (Luikart et al. 1984), bone marrow-derived mast cells (BMMC) (Razin et al. 1982; Stevens et al. 1985), and rat basophilic leukemia-1 (RBL-1) cells (Metcalfe et al. 1980b; Seldin et al. 1985). Human (MacDermott et al. 1985) and mouse (Dvorak et al. 1983) natural killer (NK) cells and rat large granular lymphocyte (LGL) tumor cells (Stevens et al. 1987) synthesize cell-associated chondroitin sulfate proteoglycans that are stored in cytolytic secretory granules.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Avraham S, Stevens RL, Gartner MC, Austen KF, Lalley PA, Weis JH (1988) Isolation of a cDNA that encodes the peptide core of the secretory granule proteoglycan of rat basophilic leukemia-1 cells and assessment of its homology to the human analogue. J Biol Chem 263:7292–7296

    PubMed  CAS  Google Scholar 

  • Benditt EP, Arase M, Roepper ME (1956) Histamine and heparin in isolated rat mast cells. J Histochem Cytochem 4:419–420

    Google Scholar 

  • Benfey PN, Yin FH, Leder P (1987) Cloning of the mast cell protease, RMCP II. Evidence for cell-specific expression and a multi-gene family. J Biol Chem 262:5377–5384

    PubMed  CAS  Google Scholar 

  • Bland CE, Ginsburg H, Silbert JE, Metcalfe DD (1982) Mouse heparin proteoglycan. Synthesis by mast cell-fibroblast monolayers during lymphocyte-dependent mast cell proliferation. J Biol Chem 257:8661–8666

    PubMed  CAS  Google Scholar 

  • Bourdon MA, Oldberg A, Pierschbacher M, Ruoslahti E (1985) Molecular cloning and sequence analysis of a chondroitin sulfate proteoglycan cDNA. Proc Natl Acad Sci USA 82:1321–1325

    Article  PubMed  CAS  Google Scholar 

  • Bourdon MA, Shiga M, Ruoslahti E (1986) Identification from cDNA of the precursor form of a chondroitin sulfate proteoglycan core protein. J Biol Chem 261:12534–12537

    PubMed  CAS  Google Scholar 

  • Bourdon MA, Krusius T, Campbell S, Schwartz NB, Ruoslahti E (1987 a) Identification and synthesis of a recognition signal for the attachment of glycosaminoglycans to proteins. Proc Natl Acad Sci USA 84:3194–3198

    Article  PubMed  CAS  Google Scholar 

  • Bourdon MA, Shiga M, Ruoslahti E (1987 b) Gene expression of the chondroitin sulfate proteoglycan core protein PG19. Mol Cell Biol 7:33–40

    PubMed  CAS  Google Scholar 

  • Caulfield JP, Hein A, Tsunoda K, Shapiro R (1986) Detection of sulfur in fixed and embedded rat peritoneal mast cell granules by X-ray energy dispersive spectroscopy. J Electron Micro Tech 3:347–356

    Article  CAS  Google Scholar 

  • Claesson L, Larhammar D, Rask L, Petserson PA (1983) cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure. Proc Natl Acad Sci USA 80:7395–7399

    Article  PubMed  CAS  Google Scholar 

  • DuBuske L, Austen KF, Czop J, Stevens RL (1984) Granule-associated serine neutral proteases of the mouse bone marrow-derived mast cell that degrade fibronectin: their increase after sodium butyrate treatment of the cells. J Immunol 133:1535–1541

    PubMed  CAS  Google Scholar 

  • Dvorak AM, Galli SJ, Marcum JA, Nabel G, der Simonian H, Goldin J, Monahan RA, Pyne K, Cantor H, Rosenberg RD, Dvorak HF (1983) Cloned mouse cells with natural killer function and cloned suppressor T cells express ultrastructural and biochemical features not shared by cloned inducer T cells. J Exp Med 157:843–861

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich P (1878) Beiträge zur Theorie und Praxis der Histologischen Färbung. Doctoral thesis, University of Leipzig, East Germany

    Google Scholar 

  • Enerbäck L (1966) Mast cells in rat gastrointestinal mucosa. 2. Dye-binding and metachromatic properties. Acta Pathol Microbiol Scand 66:303–312

    PubMed  Google Scholar 

  • Everitt MT, Neurath H (1980) Rat peritoneal mast cell carboxypeptidase: localization, purification, and enzymatic properties. FEBS Lett 110:292–296

    Article  PubMed  CAS  Google Scholar 

  • Gershenfeld HK, Weissman IL (1986) Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. Science 232:854–857

    Article  PubMed  CAS  Google Scholar 

  • Giacoletto KS, Sant AJ, Bono C, Gorka J, O’Sullivan DM, Quaranta V, Schwartz BD (1986) The human invariant chain is the core protein of the human class Il-associated proteoglycan. J Exp Med 164:1422–1439

    Article  PubMed  CAS  Google Scholar 

  • Horner AA (1971) Macromolecular heparin from rat skin. Isolation, characterization, and depolymerization with ascorbate. J Biol Chem 246:231–239

    PubMed  CAS  Google Scholar 

  • Isemura M, Ikenaka T (1975) β-Elimination and sulfite addition reaction of chondroitin sulfate peptidoglycan and the peptide structure of the linkage region. Biochim Biophys Acta 411:11–21

    Article  PubMed  CAS  Google Scholar 

  • Klickstein LB, Wintroub BU (1982) Separation of angiotensins and assay of angiotensin-generating enzymes by high-performance liquid chromatography. Ann Biochem 120:146–150

    Article  CAS  Google Scholar 

  • Kolset SO, Seljelid R, Lindahl U (1984) Modulation of the morphology and glycosaminoglycan biosynthesis of human monocytes, induced by culture substrates. Biochem J 219:793–799

    PubMed  CAS  Google Scholar 

  • Krusius T, Ruoslahti E (1986) Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci USA 83:7683–7687

    Article  PubMed  CAS  Google Scholar 

  • Lagunoff D, Pritzl P (1976) Characterization of rat mast cell granule proteins. Arch Biochem Biophys 173:554–563

    Article  PubMed  CAS  Google Scholar 

  • Levitt D, Ho PL (1983) Induction of chondroitin sulfate proteoglycan synthesis and secretion in lymphocytes and monocytes. J Cell Biol 97:351–358

    Article  PubMed  CAS  Google Scholar 

  • Lindahl U, Cifonelli JA, Lindahl B, Rodén L (1965) The role of serine in the linkage of heparin to protein. J Biol Chem 240:2817–2820

    PubMed  CAS  Google Scholar 

  • Lobe CG, Finlay BP, Paranchych W, Paetkau VH, Bleackley RC (1986) Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Science 232:858–861

    Article  PubMed  CAS  Google Scholar 

  • Luikart SD, Maniglia CA, Sartorelli AC (1984) Glycosaminoglycan synthesis during differentiation of HL60/HGPRT- leukemia cells induced by dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 44:2907–2912

    PubMed  CAS  Google Scholar 

  • MacDermott RP, Schmidt RE, Caulfield JP, Hein A, Bartley GT, Ritz J, Schlossman SF, Austen KF, Stevens RL (1985) Proteoglycans in cell-mediated cytotoxicity. Identification, localization, and exocytosis of a chondroitin sulfate proteoglycan from human cloned natural killer cells during target cell lysis. J Exp Med 162:1771–1787

    Article  PubMed  CAS  Google Scholar 

  • Metcalfe DD, Lewis RA, Silbert JE, Rosenberg RD, Wasserman SI, Austen KF (1979) Isolation and characterization of heparin from human lung. J Clin Invest 64:1537–1543

    Article  PubMed  CAS  Google Scholar 

  • Metcalfe DD, Smith JA, Austen KF, Silbert JE (1980a) Polydispersity of rat mast cell heparin. J Biol Chem 255:11753–11758

    PubMed  CAS  Google Scholar 

  • Metcalfe DD, Wasserman SI, Austen KF (1980b) Isolation and characterization of sulphated mucopolysaccharides from rat leukaemic (RBL-1) basophils. Biochem J 185:367–372

    PubMed  CAS  Google Scholar 

  • Metcalfe DD, Litvin J, Wasserman SI (1982) The isolation, identification and characterization of sulfated glycosaminoglycans synthesized in vitro by human eosinophils. Biochim Biophys Acta 715:196–204

    Article  PubMed  CAS  Google Scholar 

  • Millard PJ, Henkart MP, Reynolds CW, Henkart PA (1984) Purification and properties of cytoplasmic granules from cytotoxic rat LGL tumors. J Immunol 132:3197–3204

    PubMed  CAS  Google Scholar 

  • Muir H (1958) The nature of the link between protein and carbohydrate of a chondroitin sulphate complex from hyaline cartilage. Biochem J 69:195–204

    PubMed  CAS  Google Scholar 

  • Ogren S, Lindahl U (1975) Cleavage of macromolecular heparin by an enzyme from mouse mastocytoma. J Biol Chem 250:2690–2697

    PubMed  CAS  Google Scholar 

  • Ohhashi Y, Hasumi F, Mori Y (1984) Comparative study on glycosaminoglycans synthesized in peripheral and peritoneal polymorphonuclear leucocytes from guinea pigs. Biochem J 217:199–207

    PubMed  CAS  Google Scholar 

  • Oldberg A, Hayman EG, Ruoslahti E (1981) Isolation of a chondroitin sulfate proteoglycan from a rat yolk sac tumor and immunochemical demonstration of its cell surface location. J Biol Chem 256:10847–10852

    PubMed  CAS  Google Scholar 

  • Oldberg A, Antonsson P, Heinegård D (1987) The partial amino acid sequence of bovine cartilage proteoglycan, deduced from a cDNA clone, contains numerous Ser-Gly sequences arranged in homologous repeats. Biochem J 243:255–259

    PubMed  CAS  Google Scholar 

  • Olsson I (1969) Intracellular distribution and sites of synthesis of glycosaminoglycans (mucopolysaccharides) in human leukocytes. Exp Cell Res 54:314–317

    Article  PubMed  CAS  Google Scholar 

  • Orenstein NS, Galli SJ, Dvorak AM, Silbert JE, Dvorak HF (1978) Sulfated glycosaminoglycans of guinea pig basophilic leukocytes. J Immunol 121.586–592

    PubMed  CAS  Google Scholar 

  • Parmley RT, Rahemtulla F, Cooper MD, Rodén L (1985) Ultrastructural and biochemical characterization of glycosaminoglycans in HNK-1-positive large granular lymphocytes. Blood 66:20–25

    PubMed  CAS  Google Scholar 

  • Pasternak MS, Eisen HN (1985) A novel serine esterase expressed by cytotoxic T lymphocytes. Nature 314:743–745

    Article  Google Scholar 

  • Razin E, Stevens RL, Akiyama F, Schmid K, Austen KF (1982) Culture from mouse bone marrow of a subclass of mast cells possessing a distinct chondroitin sulfate proteoglycan with glycosaminoglycans rich in N-acetylgalactosamine-4,6-disulfate. J Biol Chem 257:7229–7236

    PubMed  CAS  Google Scholar 

  • Reynolds CW, Bere EW, Ward JM (1984) Natural killer activity in the rat. III. Characterization of transplantable large granular lymphocyte (LGL) leukemias in the F344 rat. J Immunol 132:534–540

    PubMed  CAS  Google Scholar 

  • Robinson HC, Horner AA, Höök M, Ogren S, Lindahl U (1978) A proteoglycan form of heparin and its degradation to single-chain molecules. J Biol Chem 253:6687–6693

    PubMed  CAS  Google Scholar 

  • Rodén L (1980) Structure and metabolism of connective tissue proteoglycans. In: Lennarz WJ (ed) The biochemistry of glycoproteins and proteoglycans. Plenum, New York, pp 267–371

    Google Scholar 

  • Rothenberg ME, Caulfield JP, Austen KF, Hein A, Edmiston K, Newburger PE, Stevens RL (1987) Biochemical and morphological characterization of basophilic leukocytes from two patients with myelogenous leukemia. J Immunol 138:2616–2625

    PubMed  CAS  Google Scholar 

  • Sage H, Woodbury RG, Bornstein P (1979) Structural studies on human type IV collagen. J Biol Chem 254:9893–9900

    PubMed  CAS  Google Scholar 

  • Schmidt RE, MacDermott RP, Bartley G, Bertovich M, Amato DA, Austen KF, Schlossman SF, Stevens RL, Ritz J (1985) Specific release of proteoglycans from human natural killer cells during target cell lysis. Nature 318:289–291

    Article  PubMed  CAS  Google Scholar 

  • Schmidt RE, Caulfield JP, Michon J, Hein A, Kamada MM, MacDermott RP, Stevens RL, Ritz J (1988) T11/CD2 activation of cloned human natural killer cells results in increased conjugate formation and exocytosis of cytolytic granules. J Immunol 140:991–1002

    PubMed  CAS  Google Scholar 

  • Schwartz LB, Bradford TR (1986) Regulation of tryptase from human lung mast cells by heparin. Stabilization of the active tetramer. J Biol Chem 261:7372–7379

    PubMed  CAS  Google Scholar 

  • Schwartz LB, Riedel C, Caulfield JP, Wasserman SI, Austen KF (1981) Cell association of complexes of chymase, heparin proteoglycan, and protein after degranulation by rat mast cells. J Immunol 126:2071–2078

    PubMed  CAS  Google Scholar 

  • Seldin DC, Seno N, Austen KF, Stevens RL (1984) Analysis of polysulfated chondroitin disaccharides by high-performance liquid chromatography. Ann Biochem 141:291–300

    Article  CAS  Google Scholar 

  • Seldin DC, Austen KF, Stevens RL (1985) Purification and characterization of protease-resistant secretory granule proteoglycans containing chondroitin sulfate di-B and heparin-like glycosamin-oglycans from rat basophilic leukemia cells. J Biol Chem 260:11131–11139

    PubMed  CAS  Google Scholar 

  • Serafín WE, Katz HR, Austen KF, Stevens RL (1986) Complexes of heparin proteoglycans, chondroitin sulfate E proteoglycans, and [3H]diisopropyl fluorophosphate-binding proteins are exocytosed from activated mouse bone marrow-derived mast cells. J Biol Chem 261:15017–15021

    PubMed  Google Scholar 

  • Serafín WE, Dayton ET, Gravaliese PM, Austen KF, Stevens RL (1987) Carboxypeptidase A in mouse mast cells. Identification, characterization, and use as a differentiation marker. J Immunol 139:3771–3776

    PubMed  Google Scholar 

  • Smith TJ, Hougland MW, Johnson DA (1984) Human lung tryptase. Purification and characterization. J Biol Chem 259:11046–11051

    PubMed  CAS  Google Scholar 

  • Stevens RL, Otsu K, Austen KF (1985) Purification and analysis of the core protein of the protease-resistant intracellular chondroitin sulfate E proteoglycan from the interleukin 3-dependent mouse mast cell. J Biol Chem 260:14194–14200

    PubMed  CAS  Google Scholar 

  • Stevens RL, Lee TDG, Seldin DC, Austen KF, Befus AD, Bienenstock J (1986) Intestinal mucosal mast cells from rats infected with Nippostrongylus brasiliensis contain protease-resistant chondroitin sulfate di-B proteoglycans. J Immunol 137:291–295

    PubMed  CAS  Google Scholar 

  • Stevens RL, Otsu K, Weis JH, Tantravahi RV, Austen KF, Henkart PA, Galli MC, Reynolds CW (1987) Co-sedimentation of chondroitin sulfate A glycosaminoglycans and proteoglycans with the cytolytic secretory granules of rat large granular lymphocyte (LGL) tumor cells, and identification of a mRNA in normal and transformed LGL that encodes proteoglycans. J Immunol 139:863–868

    PubMed  CAS  Google Scholar 

  • Stevens RL, Fox CC, Lichtenstein LM, Austen KF (1988 a) Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells. Proc Natl Acad Sci USA 85:2284–2287

    Article  PubMed  CAS  Google Scholar 

  • Stevens RL, Avraham S, Gartner MC, Bruns GAP, Austen KF, Weis JH (1988 b) Isolation and characterization of a cDNA that encodes the peptide core of the secretory granule proteoglycan of human promyelocytic leukemia HL-60 cells. J Biol Chem 263:7287–7291

    PubMed  CAS  Google Scholar 

  • Tantravahi RV, Stevens RL, Austen KF, Weis JH (1986) A single gene in mast cells encodes the core peptides of heparin and chondroitin sulfate proteoglycans. Proc Natl Acad Sci USA 83:9207–9210

    Article  PubMed  CAS  Google Scholar 

  • Trong HL, Neurath H, Woodbury RG (1987) Substrate specificity of the chymotrypsin-like protease in secretory granules isolated from rat mast cells. Proc Natl Acad Sci USA 84:364–367

    Article  PubMed  Google Scholar 

  • Vartio T, Seppä H, Vaheri A (1981) Susceptibility of soluble and matrix fibronectins to degradation by tissue proteinases, mast cell chymase and cathepsin G. J Biol Chem 256:471–477

    PubMed  CAS  Google Scholar 

  • Woodbury RG, Neurath H (1978) Purification of an atypical mast cell protease and its levels in developing rats. Biochemistry 17:4298–4304

    Article  PubMed  CAS  Google Scholar 

  • Young JD, Leong LG, Liu CC, Damiano A, Wall DA, Cohn ZA (1986) Isolation and characterization of a serine esterase from cytolytic T cell granules. Cell 47:183–194

    Article  PubMed  CAS  Google Scholar 

  • Yurt RW, Leid RW, Austen KF, Silbert JE (1977a) Native heparin from rat peritoneal mast cells. J Biol Chem 252:518–521

    PubMed  CAS  Google Scholar 

  • Yurt RW, Leid RW, Spragg J, Austen KF (1977b) Immunologic release of heparin from purified rat peritoneal mast cells. J Immunol 118:1201–1207

    PubMed  CAS  Google Scholar 

  • Yurt R, Austen KF (1977 c) Preparative purification of the rat mast cell chymase. Characterization and interaction with granule components. J Exp Med 146:1405–1419

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

Stevens, R.L., Kamada, M.M., Serafin, W.E. (1988). Structure and Function of the Family of Proteoglycans That Reside in the Secretory Granules of Natural Killer Cells and Other Effector Cells of the Immune Response. In: Podack, E.R. (eds) Cytotoxic Effector Mechanisms. Current Topics in Microbiology and Immunology, vol 140. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73911-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73911-8_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73913-2

  • Online ISBN: 978-3-642-73911-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics