Journal of Investigative Dermatology (1996) 106, 1075–1080; doi:10.1111/1523-1747.ep12339292
Lysozyme Binds to Elastin and Protects Elastin from Elastase-Mediated Degradation
Pyong Woo Park1, Kim Biedermann, Lisa Mecham1, Donald L Bissett and Robert P Mecham1,2
- 1Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110, U.S.A.
- The Procter and Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45253-8707, U.S.A.
- 2Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, U.S.A.
Received 29 September 1995; Revised 10 January 1996; Accepted 26 January 1996.
Top of pageAbstract
Lysozyme has been shown to be associated with damaged elastic fibers in many tissues and organs. To better characterize this interaction, binding of lysozyme to elastin was studied using solution-based binding assays. Under physiologic conditions, radio-labeled lysozyme bound specifically to elastin in a time- and concentration-dependent manner. Binding was reversible and was inhibited by unlabeled human and hen lysozyme but not by other proteins. Lysozyme had no elastolytic activity as assessed by a standard tritium-release assay, but, importantly, prevented the proteolytic degradation of elastin by human leukocyte elastase, pancreatic elastase, thermolysin, and Pseudomonas elastase. A striking feature of lysozyme's anti-elastase activity was that it did not function in the classical sense of inhibiting directly the enzymatic activity of the protease. Instead, by binding to elastin, lysozyme prevented the protease from interacting with the elastin substrate in ways that normally favor proteolysis. These results show that lysozyme binds to the elastin component of elastic fibers and that this interaction has important biological consequences for elastic fiber degradation. By preventing degradation of elastin, lysozyme can function as an important natural inhibitor that exerts a protective effect on elastic fibers at sites of tissue injury.
Keywords:
elastolysis, protection, assembly, elastase
Top of pageReferences
- Albrecht, S, From, L, Kahn, HJ: Lysozyme in abnormal dermal elastic fibers of cutaneous aging, solar elastosis, and pseudoxanthoma elasticum. J Cutan Pathol 18: 75–80, 1991
- Banda, MJ, Dovey, HF, Werb, Z: Elastinolytic enzymes. In: Adams DO, Edelson PJ, Koren II (eds.). Methods for studying Mononuclear phagocytes Academic Press, New York, pp 603–618, 1981
- Beith, JG: Elastases: catalytic and biological properties. In: Mecham RP (ed.). Regulation of Matrix Accumulation Academic Press, New York, pp 217–320, 1986
- Breathnach, SM, Melrose, SM, Bhogal, B, de Beer, FC, Dyck, RF, Tennent, G, Black, MM, Pepys, MB: Amyloid P component is located on elastic libre microfibrils in normal human tissue. Nature 293: 652–654, 1981 | Article | PubMed | ChemPort |
- Breathnach, SM, Pepys, MF, Hintner, H: Tissue amyloid P component in normal human dermis is non-covalently associated with elastic fiber microfibrils. J Invest Dermatol 92: 53–58, 1989
- Bertz, U, Baggolini, M: Biochemical and morphometrical characterization of azuruphil and specific granules of human neutrophilic polymorphonuclear leukocytes. J Cell Biol 63: 251–269, 1974
- Chapman, HA, Munger, JS, Shi, G: The role of thiol proteases in tissue injury and remodeling. Am J Respir Crit Care Med 150: 155–159, 1994
- Dahlbäck, K, Löfberg, H, Aluments, J, Dahlbäck, B: Immunohistochemical demonstration of age-related deposition of vitronectin (S-protein of complement) and terminal complement complex on dermal elastic fibers. J Invest Dermatol 92: 727–733, 1989
- Davies, JD, Young, EW, Mera, SL, Barnard, K: Lysozyme is a component of human vascular elastic fibers. Experientia 39: 382–383, 1983
- Galloway, DR: Pseudomonas aeruginosa elastase and elastolysis revisited: recent developments. Mol Microbiol 5: 2315–2321, 1991
- Gibson, MA, Sandberg, LB, Grosso, LE, Cleary, EG: Complementary DNA cloning establishes microfibril-associated glycoprotein (MAGP) to be a discrete component of the elastin-associated microfibrils. J Biol Chem 266: 7596–7601, 1991
- Horrigan, SK, Rich, CB, Streeten, BW, Li, ZY, Foster, JA: Characterization of an associated microfibril protein through recombinant DNA techniques. J Biol Chem 267: 10087–10095, 1992
- Jollès, P, Jollès, J: What's new in lysozyme research? Always a model system, today as yesterday. Mol Cell Biochem 63: 165–189, 1984
- Kagan, HM, Crombie, GD, Jordan, RE, Lewis, W, Franzblau, C: Proteolysis of elastin-ligand complexes. Stimulation of elastase digestion of insoluble elastin by sodium dodecyl sulfate. Biochemistry 11: 3412–3418, 1972
- Kagan, HM, Jordan, RE, Lerch, RM, Mukherjee, DP, Stone, P, Franzblau, C: Factors affecting the proteolytic degradation of elastin. Adv Exp Med Biol 79: 189–207, 1977
- Köbsel, N, Ramadori, G: Human hepatoma cells synthesize and secrete lysozyme: modulation by cytokines. Hepatology 19: 1182–1188, 1994
- Krivan, HC, Roberts, DD, Ginsburg, V: Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc
1-4Gal found in some glycolipids. Proc Natl Acad Sci USA 85: 6157–6161, 1988 | PubMed | ChemPort | - Kuhn, C. III, Yu, S, Chraplyvy, M, Linder, HE, Senior, RM: The induction of emphysema with elastase. II. Changes in connective tissue. Lab Invest 34: 372–380, 1976
- Lansing, AI, Roberts, E, Ramasarma, GB, Rosenthal, TB, Alex, M: Changes with age in amino acid composition of arterial elastin. Proc Soc Exp Biol Med 76: 714–717, 1951 | PubMed | ISI | ChemPort |
- Lavker, RM, Gerberick, GF, Veres, D, Irwin, CJ, Kaidbey, KH: Cumulative effects from repeated exposures to suberythmal doses of UVB and UVA in human skin. J Am Acad Dermatol 32: 53–62, 1995
- Li, ZY, Wallace, RN, Streeten, BW, Dark, AJ: Elastic fiber components and protease inhibitors in pinguecula. Invest Ophthalmol Vis Sci 32: 1573–1585, 1991
- Mecham, RP, Davis, EC: Elastic fiber structure and assembly. In: Yurchenko PD, Brik DE, Mecham RP (eds.). Extracellular Matrix Assembly and Structure Academic Press, San Diego, pp 281–314, 1994
- Mecham, RP, Heuser, J: Substructure of elastic fibers as viewed by quick freeze, deep etch microscopy. In: Hay ED (ed). Cell Biology Extracellular Matrix Plenum Press, New York, pp 79–109, 1991
- Mera, SL, Davies, JD: Elastosis in breast carcinoma: I. Immunohistchemical characterization of elastic fibres. J Pathol 151: 103–110, 1987
- Mera, SL, Lovell, CR, Jones, R, Davies, JD: Elastic fibres in normal and sun-damaged skin: an immunohistochemical study. Br J Dermatol 117: 21–27, 1987 | PubMed | ISI | ChemPort |
- Murphy, G, Cockett, MI, Ward, RV, Docherty, AJP: Matrix metalloproteinase degradation of elastin, type IV collagen, and proteoglycan. Biochem J 227: 277–279, 1991
- Potempa, J, Dubin, A, Korzus, G, Travis, J: Degradation of elastin by a cysteine proteinase from staphylococcus aureus. J Biol Chem 263: 2664–2667, 1988
- Prosser, IW, Gibson, MA, Cleary, EG: Microfibrillar protein from elastic tissue: a critical evaluation. Aust J Exp Biol Med Sci 62: 485–505, 1984
- Resnitzky, P, Shaft, D, Yaari, A, Nir, E: Distinct intracellular lysozyme content in normal granulocytes and monocytes: a quantitative immunoperoxidase and ultrastructural immunogold study. J Histochem Cytochem 42: 1471–1477, 1994
- Rosenbloom, J, Abrams, WR, Mecham, RP: Extracellular matrix 4: the elastic fiber. FASEB J 7: 1208–1218, 1993 | PubMed | ISI | ChemPort |
- Sakai, LY, Keene, DR, Engvall, E: Fibrillin, a new 350-kD glycoprotein, is a companent of extracellular microfibrils. J Cell Biol 103: 2499–2509, 1986 | Article | PubMed | ISI | ChemPort |
- Schwartz, E, Godlfischer, S, Coltoff-Schiller, B, Blumenfeld, OO: Extracellular matrix microfibrils are composed of core proteins coated with fibronectin. J Histochem Cytochem 33: 268–274, 1985
- Senior, RM, Griffin, GL, Fliszar, CJ, Shapiro, SD, Goldberg, GI, Welgus, HG: Human 92-and 72-kilodalton type IV collagenases are elastases. J Biol Chem 266: 7870–7875, 1991 | PubMed | ISI | ChemPort |
- Shapiro, SD, Griffin, GL, Gilbert, DJ, Jenkins, NA, Copeland, NG, Welgus, HG, Senior, RM, Ley, TJ: Molecular cloning, chromosomal localization, and bacterial expression of a murine macrophage metalloelastase. J Biol Chem 267: 4664–4671, 1992 | PubMed | ISI | ChemPort |
- Takeuchi, K, Irwin, DM, Gallup, M, Shinbort, E, Kai, H, Stewart, CB, Basbaum, C: Multiple cDNA sequences of bovine tracheal lysozyme. J Biol Chem 268: 27440–27446, 1993
- Taomasini-Johansson, BR, Ruoslahti, E, Peirsehbacher, MD: A 30 kD sulfated extracellular matrix protein immunologically crossreactive with vitronectin. Matrix 13: 203–214, 1993
- Travis, J, Salvensen, GS: Human plasma proteins inhibitors. Annu Rev Biochem 52: 655–709, 1983 | Article | PubMed | ISI |