Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Jan;79(1):188–197. doi: 10.1172/JCI112782

Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects.

S C Christiansen, D Proud, C G Cochrane
PMCID: PMC424020  PMID: 3540008

Abstract

Kininogenase activity was detected by cleavage of radiolabeled substrate (125I-high molecular weight kininogen [HMWK]) in 22 of 24 bronchoalveolar lavage (BAL) fluid samples from 17 asthmatics who either responded to aerosolized allergen challenge or had symptoms of active asthma. In contrast, six of seven normal controls lacked enzymatic activity. Levels of free immunoreactive kinin found in BAL fluid correlated with the presence of kininogenase activity (P = 0.002). The cleavage pattern of 125I-HMWK by the BAL fluid kininogenase (a dominant 65,000-mol wt fragment), and synthetic inhibitor profile (phe-phe-arg-CH2Cl and phenylmethylsulfonyl fluoride) were compatible with a tissue kallikrein. Peak kininogenase activity eluted at an apparent molecular weight of 20,000-34,000 by HPLC gel filtration. Its antigenic identity was established by immunoblotting with anti-human urinary kallikrein antibody and its activity was inhibited by this antibody. Lysylbradykinin was generated during incubation of fractionated BAL fluid and purified HMWK, the characteristic cleavage product of the tissue kallikreins. We conclude that elevated amounts of tissue kallikrein and kinin are present in the bronchoalveolar spaces of asthmatic subjects. Kinin generation may contribute to the asthmatic response directly through edema formation and smooth muscle contraction and by augmenting release and/or production of preformed (histamine) and secondary mediators such as leukotrienes and platelet-activating factor.

Full text

PDF
188

Images in this article

192Image
on p.192
192Image
on p.192
192Image
on p.192
193Image
on p.193
194Image
on p.194
194Image
on p.194
194Image
on p.194
194Image
on p.194
194Image
on p.194

Selected References

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

  1. Baugh R. J., Travis J. Human leukocyte granule elastase: rapid isolation and characterization. Biochemistry. 1976 Feb 24;15(4):836–841. doi: 10.1021/bi00649a017. [DOI] [PubMed] [Google Scholar]
  2. Baumgarten C. R., Nichols R. C., Naclerio R. M., Proud D. Concentrations of glandular kallikrein in human nasal secretions increase during experimentally induced allergic rhinitis. J Immunol. 1986 Aug 15;137(4):1323–1328. [PubMed] [Google Scholar]
  3. Bell R. L., Baenziger N. L., Majerus P. W. Bradykinin-stimulated release of arachidonate from phosphatidyl inositol in mouse fibrosarcoma cells. Prostaglandins. 1980 Aug;20(2):269–274. doi: 10.1016/s0090-6980(80)80045-1. [DOI] [PubMed] [Google Scholar]
  4. Carretero O. A., Oza N. B., Piwonska A., Ocholik T., Scicli A. G. Measurement of urinary kallikrein activity by kinin radioimmunoassay. Biochem Pharmacol. 1976 Oct 15;25(20):2265–2270. doi: 10.1016/0006-2952(76)90008-3. [DOI] [PubMed] [Google Scholar]
  5. Cochrane C. G., Griffin J. H. The biochemistry and pathophysiology of the contact system of plasma. Adv Immunol. 1982;33:241–306. doi: 10.1016/s0065-2776(08)60837-8. [DOI] [PubMed] [Google Scholar]
  6. Eggleston P. A., Kagey-Sobotka A., Schleimer R. P., Lichtenstein L. M. Interaction between hyperosmolar and IgE-mediated histamine release from basophils and mast cells. Am Rev Respir Dis. 1984 Jul;130(1):86–91. doi: 10.1164/arrd.1984.130.1.86. [DOI] [PubMed] [Google Scholar]
  7. Field M., Musch M. W., Miller R. L., Goetzl E. J. Regulation of epithelial electrolyte transport by metabolites of arachidonic acid. J Allergy Clin Immunol. 1984 Sep;74(3 Pt 2):382–385. doi: 10.1016/0091-6749(84)90135-0. [DOI] [PubMed] [Google Scholar]
  8. Fuller R. W., Dixon C. M., Dollery C. T., Barnes P. J. Prostaglandin D2 potentiates airway responsiveness to histamine and methacholine. Am Rev Respir Dis. 1986 Feb;133(2):252–254. doi: 10.1164/arrd.1986.133.2.252. [DOI] [PubMed] [Google Scholar]
  9. Geiger R., Hofmann W., Franke M., Baur X. Biochemistry of human tissue kallikrein. Adv Exp Med Biol. 1983;156:275–288. [PubMed] [Google Scholar]
  10. Ishizaka T., Iwata M., Ishizaka K. Release of histamine and arachidonate from mouse mast cells induced by glycosylation-enhancing factor and bradykinin. J Immunol. 1985 Mar;134(3):1880–1887. [PubMed] [Google Scholar]
  11. Kato H., Nagasawa S., Iwanaga S. HMW and LMW kininogens. Methods Enzymol. 1981;80(Pt 100):172–198. doi: 10.1016/s0076-6879(81)80017-1. [DOI] [PubMed] [Google Scholar]
  12. Kerbiriou D. M., Griffin J. H. Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma. J Biol Chem. 1979 Dec 10;254(23):12020–12027. [PubMed] [Google Scholar]
  13. Kettner C., Shaw E. Inactivation of trypsin-like enzymes with peptides of arginine chloromethyl ketone. Methods Enzymol. 1981;80(Pt 100):826–842. doi: 10.1016/s0076-6879(81)80065-1. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Maier M., Austen K. F., Spragg J. Kinetic analysis of the interaction of human tissue kallikrein with single-chain human high and low molecular weight kininogens. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3928–3932. doi: 10.1073/pnas.80.13.3928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maier M., Spragg J., Schwartz L. B. Inactivation of human high molecular weight kininogen by human mast cell tryptase. J Immunol. 1983 May;130(5):2352–2356. [PubMed] [Google Scholar]
  18. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  19. McIntyre T. M., Zimmerman G. A., Satoh K., Prescott S. M. Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate. J Clin Invest. 1985 Jul;76(1):271–280. doi: 10.1172/JCI111957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meier H. L., Kaplan A. P., Lichtenstein L. M., Revak S., Cochrane C. G., Newball H. H. Anaphylactic release of a prekallikrein activator from human lung in vitro. J Clin Invest. 1983 Aug;72(2):574–581. doi: 10.1172/JCI111005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mori K., Sakamoto W., Nagasawa S. Studies on human high molecular weight (HMW) kininogen. III. Cleavage of HMW kininogen by the action of human salivary kallikrein. J Biochem. 1981 Aug;90(2):503–509. doi: 10.1093/oxfordjournals.jbchem.a133498. [DOI] [PubMed] [Google Scholar]
  22. Nagase H., Barrett A. J. Human plasma kallikrein. A rapid purification method with high yield. Biochem J. 1981 Jan 1;193(1):187–192. doi: 10.1042/bj1930187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Newball H. H., Berninger R. W., Talamo R. C., Lichtenstein L. M. Anaphylactic release of a basophil kallikrein-like activity. I. Purification and characterization. J Clin Invest. 1979 Aug;64(2):457–465. doi: 10.1172/JCI109483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Newball H. H., Talamo R. C., Lichtenstein L. M. Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions. J Clin Invest. 1979 Aug;64(2):466–475. doi: 10.1172/JCI109484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Orehek J., Gayrard P., Smith A. P., Grimaud C., Charpin J. Airway response to carbachol in normal and asthmatic subjects: distinction between bronchial sensitivity and reactivity. Am Rev Respir Dis. 1977 Jun;115(6):937–943. doi: 10.1164/arrd.1977.115.6.937. [DOI] [PubMed] [Google Scholar]
  26. Proud D., MacGlashan D. W., Jr, Newball H. H., Schulman E. S., Lichtenstein L. M. Immunoglobulin E-mediated release of a kininogenase from purified human lung mast cells. Am Rev Respir Dis. 1985 Aug;132(2):405–408. doi: 10.1164/arrd.1985.132.2.405. [DOI] [PubMed] [Google Scholar]
  27. Proud D., Togias A., Naclerio R. M., Crush S. A., Norman P. S., Lichtenstein L. M. Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen. J Clin Invest. 1983 Nov;72(5):1678–1685. doi: 10.1172/JCI111127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Silver M. R., ole-MoiYoi O., Austen K. F., Spragg J. Active site radioimmunoassay for human urokallikrein and demonstration by radioimmunoassay of a latent form of the enzyme. J Immunol. 1980 Apr;124(4):1551–1555. [PubMed] [Google Scholar]
  29. Togias A. G., Naclerio R. M., Proud D., Fish J. E., Adkinson N. F., Jr, Kagey-Sobotka A., Norman P. S., Lichtenstein L. M. Nasal challenge with cold, dry air results in release of inflammatory mediators. Possible mast cell involvement. J Clin Invest. 1985 Oct;76(4):1375–1381. doi: 10.1172/JCI112113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Twumasi D. Y., Liener I. E. Proteases from purulent sputum. Purification and properties of the elastase and chymotrypsin-like enzymes. J Biol Chem. 1977 Mar 25;252(6):1917–1926. [PubMed] [Google Scholar]
  32. Varonier H. S., Panzani R. The effect of inhalations of bradykinin on healthy and atopic (asthmatic) children. Int Arch Allergy Appl Immunol. 1968;34(3):293–296. doi: 10.1159/000230120. [DOI] [PubMed] [Google Scholar]
  33. Wintroub B. U., Kaempfer C. E., Schechter N. M., Proud D. A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization. J Clin Invest. 1986 Jan;77(1):196–201. doi: 10.1172/JCI112276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wong P. Y., Westlund P., Hamberg M., Granström E., Chao P. H., Samuelsson B. 15-Lipoxygenase in human platelets. J Biol Chem. 1985 Aug 5;260(16):9162–9165. [PubMed] [Google Scholar]

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

RESOURCES