Skip to main content
SpringerLink
Log in

The Plasma Serine Protease Inhibitors (Serpins): Structural Modifications in Inflammation

  • Chapter
Acute Phase Proteins in the Acute Phase Response

Part of the book series: Argenteuil Symposia ((ARGENTEUIL))

Abstract

The serine protease inhibitor (serpin) superfamily comprises more than 20 glycoproteins that show primary sequence homology at protein or cDNA level with the archetype of the family, α1-antitrypsin (abbreviated hereafter to antitrypsin). Members of the family are presumed to be derived by divergent evolution from a common ancestral protein over a period of more than 500 million years (Hunt and Dayhoff 1980; Carrell and Boswell 1986). Although the serpins are widely distributed in nature, and have been identified in viruses and plants, the best studied members of the family are the human plasma serpins (Table 9.1). Most plasma serpins function as inhibitors of serine proteases and are principally involved in inflammation, controlling the activities of enzymes that trigger the inflammatory cascades including coagulation, fibrinolysis, complement activation and kinin release. However some serpins have apparently lost their antiprotease activity and have evolved other functions, such as hormone binding in the case of thyroxine binding globulin (TBG) and cortisol binding globulin (CBG).

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

Access this chapter

Log in via an institution
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 EPUB and 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

  • Babior BM (1978) Oxygen-dependent microbial killing by phagocytes. N Engl J Med 298: 659–668

    Article  PubMed  CAS  Google Scholar 

  • Banda MJ, Clark EJ, Sinha S, Travis J (1987) Interaction of mouse macrophage elastase with native and oxidised human α1-proteinase inhibitor. J Clin Invest 79: 1314–1317

    Article  PubMed  CAS  Google Scholar 

  • Banda MJ, Rice AG, Griffin GL, Senior RM (1988) α1-Proteinase inhibitor is a neutrophil chemoattractant after proteolytic inactivation by macrophage elastase. J Biol Chem 263: 4481–4484

    Google Scholar 

  • Bathurst IC, Errington DM, Foreman RC, Judah JD, Carrell RW (1985) Human Z α1-antitrypsin accumulates intracellular and stimulates lysosomal activity when synthesised in the xenopus oocyte. FEBS Lett 183: 304–308

    Article  PubMed  CAS  Google Scholar 

  • Carlson JA, Rogers BB, Sifers RN et al. (1988) PiZ α1-antitrypsin causes liver disease in transgenic mice. J Clin Invest 82: 26–36

    Article  PubMed  CAS  Google Scholar 

  • Carp H, Janoff A (1980) Potential mediator of inflammation. Phagocyte-derived oxidants suppress the elastase-inhibitory capacity of α1-proteinase inhibitor in vitro. J Clin Invest 66: 987–995

    Article  PubMed  CAS  Google Scholar 

  • Carp H, Miller F, Hoidal JR, Janoff A (1982) Potential mechanism of emphysema: α1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidised methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci USA 79: 2041–2045

    Article  PubMed  CAS  Google Scholar 

  • Carp H, Janoff A, Abrams W et al. (1983) Human methionine sulfoxide-peptide reductase, an enzyme capable of reactivating oxidised α1-proteinase inhibitor in vitro. Am Rev Respir Dis 127: 301–305

    PubMed  CAS  Google Scholar 

  • Carrell RW, Boswell DR (1986) Serpins: a family of serine proteinase inhibitors. In: Barrett A, Salvesen G (eds) Protease inhibitors. Elsevier, Amsterdam, pp 403–420

    Google Scholar 

  • Carrell RW, Owen MC (1985) Plakalbumin, α1-antitrypsin, antithrombin and the mechanism of inflammatory thrombosis. Nature 317: 730–732

    Article  PubMed  CAS  Google Scholar 

  • Carrell RW, Jeppsson JO, Laurell CB et al. (1982) Structure and variation of human α1-antitrypsin. Nature 298: 329–334

    Article  PubMed  CAS  Google Scholar 

  • Desrochers PE, Weiss SJ (1988) Proteolytic inactivation of α1-proteinase inhibitor by a neutrophil metalloproteinase. J Clin Invest 81: 1646–1650

    Article  PubMed  CAS  Google Scholar 

  • Duswald KH, Jochum M, Schramm W, Fritz H (1985) Released granulocytic elastase: an indicator of pathobiochemical alterations in septicaemia after abdominal surgery. Surgery 98: 892–899

    PubMed  CAS  Google Scholar 

  • Eriksson S, Carlson J, Velez R (1986) Risk of cirrhosis and primary liver cancer in α1-antitrypsin deficiency. N Engl J Med 314: 736–739

    Article  PubMed  CAS  Google Scholar 

  • Ganrot K (1974) The plasma protein patterns in acute infectious diseases. Scand J Clin Lab Invest 34: 75–81

    Article  PubMed  CAS  Google Scholar 

  • George PM, Vissers MCM, Travis J, Winterbourn CC, Carrell RW (1984) A genetically engineered mutant of α1-antitrypsin protects connective tissue from neutrophil damage and may be useful in lung disease. Lancet ii: 1426–1428

    Google Scholar 

  • Hunt LT, Dayhoff MO (1980) A surprising new protein superfamily containing ovalbumin, antithrombin-III and at-proteinase inhibitor. Biochem Biophys Res Commun 95: 864–871

    Article  PubMed  CAS  Google Scholar 

  • Johnson D, Travis J (1977) Inactivation of human α1-proteinase inhibitor by thiol proteinases. Biochem J 163: 639–641

    PubMed  CAS  Google Scholar 

  • Johnson D, Travis J (1979) The oxidative inactivation of human α1-proteinase inhibitor. Further evidence for methionine at the reactive center. J. Biol Chem 254: 4022–4026

    PubMed  CAS  Google Scholar 

  • Kageyama R, Ohkubo H, Nakanishi S (1985) Induction of rat liver angiotensinogen mRNA following acute inflammation. Biochem Biophys Res Commun 129: 826–832

    Article  PubMed  CAS  Google Scholar 

  • Kress LF (1986) Inactivation of human plasma serine proteinase inhibitors (serpins) by limited proteolysis of the reactive site loop with snake venom and bacterial metalloproteinases. J Cell Biochem 32: 51–58

    Article  PubMed  CAS  Google Scholar 

  • Kress LF, Catanese J J (1981) Identification of the cleavage sites resulting from enzymatic inactivation of human antithrombin III by Crotalus adamanteus proteinase II in the presence and absence of heparin. Biochemistry 20: 7432–7438

    Article  PubMed  CAS  Google Scholar 

  • Kress LF, Kurecki T, Chan SK, Laskowski M (1979) Characterisation of the inactive fragment resulting from limited proteolysis of human α1-proteinase inhibitor by Crotalus adamanteus proteinase II. J Biol Chem 254: 5317–5320

    PubMed  CAS  Google Scholar 

  • Laskowski M, Kato I (1980) Protein inhibitors of proteinases. Annu Rev Biochem 49: 593–626

    Article  PubMed  CAS  Google Scholar 

  • Laurell CB, Eriksson S (1963) The electrophoretic α1-globulin pattern of serum in α1-antitrypsin deficiency. Scand J Clin Lab Invest 15: 132–140

    CAS  Google Scholar 

  • Liebermann J (1973) Heat lability of α1-antitrypsin variants. Chest 64: 579–584

    Article  Google Scholar 

  • Liebermann J (1976) Elastase, collagenase, emphysema and α1-antitrypsin deficiency. Chest 70: 62–67

    Article  Google Scholar 

  • Linderstrom-Lang KU (1952) The enzymatic breakdown of ovalbumin. Med Sci 6: 73–92

    Google Scholar 

  • Loebermann H, Tokuoka R, Deisenhofer J, Huber R (1984) Human α1-proteinase inhibitor: crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J Mol Biol 177: 531–556

    Article  PubMed  CAS  Google Scholar 

  • Morihara K, Tsusuki H, Harada M, Iwato T (1984) Purification of human plasma α1-proteinase inhibitor and its inactivation by Pseudomonas aeruginosa elastase. J Biochem 95: 795–804

    PubMed  CAS  Google Scholar 

  • Owen MC, Brennan SO, Lewis JH, Carrell RW (1983) Mutation of antitrypsin to antithrombin. α1-Antitrypsin Pittsburgh (358 Met→Arg), a fatal bleeding disorder. N Engl J Med 309: 694–698

    Article  PubMed  CAS  Google Scholar 

  • Owens MR, Miller LL (1980) Net biosynthesis of antithrombin III by the isolated rat liver perfused for 12-24 hours. Biochim Biophys Acta 627: 30–39

    Article  PubMed  CAS  Google Scholar 

  • Pemberton PA, Stein PE, Pepys MB, Potter JM, Carrell RW (1988) Hormone binding globulins undergo serpin conformational change in inflammation. Nature 336: 257–258

    Article  PubMed  CAS  Google Scholar 

  • Pemberton PA, Harrison RA, Lachmann PJ, Carrell RW (1989) The structural basis for neutrophil inactivation of C1-inhibitor. Biochem J 258: 193–198

    PubMed  CAS  Google Scholar 

  • Perlmutter DH, Schlesinger MJ, Pierce JA, Schwartz AL (1988) Intracellular accumulation of α1-antitrypsin (α1AT) in PiZZ α1AT deficiency with constitutive expression of heat shock genes. Clin Res 36: 611A

    Google Scholar 

  • Potempa J, Watorek W, Travis J (1986) The inactivation of human plasma α1-proteinase inhibitor by proteinases from Staphylococcus aureus. J Biol Chem 261: 14330–14334

    PubMed  CAS  Google Scholar 

  • Potempa J, Shieh BH, Travis J (1988) α2-Antiplasmin: a serpin with 2 separate but overlapping reactive sites. Science 241: 699–700

    Google Scholar 

  • Rosenberg S, Barr PJ, Najarian RC, Hallewell RA (1984) Synthesis in yeast of a functional, oxidation resistant active centre variant of human α1-antitrypsin. Nature 312: 77–80

    Article  PubMed  CAS  Google Scholar 

  • Salvesen GS, Catanese JJ, Kress LF, Travis J (1985) Primary structure of the reactive site of human C1-inhibitor. J Biol Chem 260: 2432–2436

    PubMed  CAS  Google Scholar 

  • Samama JP, Delarue M, Moras D, Petitou M, Lormeau JC, Choay J (1987) Crystallographic investigation of antithrombin III (Abstract 966). Thromb Haemost 58: 264

    Google Scholar 

  • Savu L, Zouaghi H, Carli A, Nunez EA (1981) Serum depletion of corticosteroid binding activities, an early marker of human septic shock. Biochem Biophys Res Commun 102: 411–419

    Article  PubMed  CAS  Google Scholar 

  • Schindler D (1984) In: Ahmad S, Black S, Schulz J, Scott W, Whelan J (eds) 16th Miami winter symposium. Advances in gene technology, human genetic disorders, p 32

    Google Scholar 

  • Scultze HE, Heide K, Haupt H (1962) α1-Antitrypsin aus Humanserum. Klin Wochenschr 8: 428–434

    Google Scholar 

  • Skeggs LT, Marsh WH, Khan JR, Shumaray NP (1954) The existence of two forms of hypertension. J Exp Med 99: 275–282

    Article  PubMed  CAS  Google Scholar 

  • Skeggs LT, Lentz KE, Gould AB et al. (1967) Biochemistry and kinetics of the renin-angiotensin system. Fed Proc 26: 42–47

    PubMed  CAS  Google Scholar 

  • Sveger T, Thelin T (1981) Four-year-old children with α1-antitrypsin deficiency. Acta Paediatr Scand 70: 171–177

    Article  PubMed  CAS  Google Scholar 

  • Travis J, Salvesen GS (1983) Human plasma proteinase inhibitors. Annu Rev Biochem 52: 655–709

    Article  PubMed  CAS  Google Scholar 

  • Travis J, Salvesen GS, Matheson NR (1987) The use of association rate constants in determining the specificity of proteinase inhibitors. In: Cunningham DD, Long GL (eds) Proteases in biological control and biotechnology. Alan R. Liss, New York, pp 307–310

    Google Scholar 

  • Vaughan L, Carrell R (1981) α1-antitrypsin isoforms: structural basis of microheterogeneity. Biochem Int 2: 461–467

    Google Scholar 

  • Vaughan L, Lorier MA, Carrell RW (1982) α1-antitrypsin microheterogeneity. Isolation and physiological significance of isoforms. Biochim Biophys Acta 701: 339–345

    Google Scholar 

  • Virca GD, Lyerly D, Kreger A, Travis J (1982) Inactivation of human plasma α1-proteinase inhibitor by a metalloproteinase from Serratia marcescens. Biochim Biophys Acta 704: 267–271

    Article  PubMed  CAS  Google Scholar 

  • Vissers MCM, George PM, Bathurst IC, Brennan SO, Winterbourn CC (1988) Cleavage and inactivation of α1-antitrypsin by metalloproteinases released from neutrophils. J Clin Invest 82: 706–711

    Article  PubMed  CAS  Google Scholar 

  • Weissmann G, Smolen JE, Korchak HM (1980) Release of inflammatory mediators from stimulated neutrophils. N Engl J Med 303: 27–34

    Article  PubMed  CAS  Google Scholar 

  • Westaby S (1983) Complement and the damaging effects of cardiopulmonary bypass. Thorax 38: 321–325

    Article  PubMed  CAS  Google Scholar 

  • Wintroub BU, Klickstein LB, Dzau VJ, Watt KWK (1984) Granulocyte-angiotensin system. Identification of angiotensinogen as the plasma protein substrate of leukocyte cathepsin G. Biochemistry 23: 227–232

    Article  CAS  Google Scholar 

  • Wright HT (1984) Ovalbumin is an elastase substrate. J Biol Chem 259: 14335–14336

    PubMed  CAS  Google Scholar 

  • Zouaghi H, Savu L, Delorme J, Kleinknecht D, Nunez EA (1983) Loss of serum transcortin in human shock associated with severe infection by Candida albicans. Acta Endocrinol (Copenh) 102: 277–283

    CAS  Google Scholar 

Download references

Authors
  1. P. E. Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. W. Carrell
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Immunological Medicine Unit, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, W12 0NN, London, UK

    M. B. Pepys MA, MD, PhD, FRCP, MCRPath

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag London Limited

About this chapter

Cite this chapter

Stein, P.E., Carrell, R.W. (1989). The Plasma Serine Protease Inhibitors (Serpins): Structural Modifications in Inflammation. In: Pepys, M.B. (eds) Acute Phase Proteins in the Acute Phase Response. Argenteuil Symposia. Springer, London. https://doi.org/10.1007/978-1-4471-1739-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-1739-1_9

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-1741-4

  • Online ISBN: 978-1-4471-1739-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation