Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Dec;88(6):1969–1975. doi: 10.1172/JCI115522

Mitogenic effect of lysosomal hydrolases on bovine tracheal myocytes in culture.

D B Lew 1, M C Rattazzi 1
PMCID: PMC295779  PMID: 1836469

Abstract

Studies were conducted to assess the mitogenic effect of lysosomal hydrolases, enzymes known to have an association with allergen- or ozone-induced airway hyperreactivity, on bovine tracheal myocytes in culture. Addition of purified human placental beta-hexosaminidase and partially purified bovine liver beta-glucuronidase resulted in the doubling of cell count after 4 d of incubation in medium M199 with 0.4% FBS. Unstimulated cells remained quiescent without a significant increase of cell count. Lysosomal hydrolases also selectively enhanced 3H-thymidine incorporation four to seven times more than that in vehicle-treated cells or cells treated with endotoxin, a common contaminant of purified enzymes. Ovalbumin (glycoprotein control), pronase, and lysozyme caused a modest but statistically insignificant increase (up to twofold) in 3H-thymidine incorporation. Elastase, collagenase and dialyzed E. coli beta-glucuronidase had no effect. The mitogenic effect of hydrolases was equally seen in quiescent, serum-depleted cells as well as in those maintained in medium with 10% FBS, suggesting that it was independent of serum factors. The effect of lysosomal hydrolases was inhibited by exposure to yeast mannan, and mannosylated human serum albumin had a mitogenic effect, suggesting the involvement of a mannose receptor. We conclude that lysosomal hydrolases may play a role in the development of the hyperplasia/hypertrophy of respiratory smooth muscle.

Full text

PDF
1969

Images in this article

1971Image
on p.1971
1971Image
on p.1971

Selected References

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

  1. Armour C. L., Diment L. M., Black J. L. Relationship between smooth muscle volume and contractile response in airway tissue. Isometric versus isotonic measurement. J Pharmacol Exp Ther. 1988 May;245(2):687–691. [PubMed] [Google Scholar]
  2. Barnes P. J. Inflammatory mediator receptors and asthma. Am Rev Respir Dis. 1987 Jun;135(6 Pt 2):S26–S31. doi: 10.1164/arrd.1987.135.6P2.S26. [DOI] [PubMed] [Google Scholar]
  3. Bousquet J., Chanez P., Lacoste J. Y., Barnéon G., Ghavanian N., Enander I., Venge P., Ahlstedt S., Simony-Lafontaine J., Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. doi: 10.1056/NEJM199010113231505. [DOI] [PubMed] [Google Scholar]
  4. Clohisy D. R., Chappel J. C., Teitelbaum S. L. Bone marrow-derived mononuclear phagocytes autoregulate mannose receptor expression. J Biol Chem. 1989 Apr 5;264(10):5370–5377. [PubMed] [Google Scholar]
  5. Conzelmann E., Sandhoff K. Purification and characterization of an activator protein for the degradation of glycolipids GM2 and GA2 by hexosaminidase A. Hoppe Seylers Z Physiol Chem. 1979 Dec;360(12):1837–1849. doi: 10.1515/bchm2.1979.360.2.1837. [DOI] [PubMed] [Google Scholar]
  6. Dohlman J. G., Payan D. G., Goetzl E. J. Generation of a unique fibroblast-activating factor by human monocytes. Immunology. 1984 Jul;52(3):577–584. [PMC free article] [PubMed] [Google Scholar]
  7. Dunnill M. S., Massarella G. R., Anderson J. A. A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema. Thorax. 1969 Mar;24(2):176–179. doi: 10.1136/thx.24.2.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Glaser J. H., Roozen K. J., Brot F. E., Sly W. S. Multiple isoelectric and recognition forms of human beta-glucuronidase activity. Arch Biochem Biophys. 1975 Feb;166(2):536–542. doi: 10.1016/0003-9861(75)90417-8. [DOI] [PubMed] [Google Scholar]
  9. Kornfeld S., Mellman I. The biogenesis of lysosomes. Annu Rev Cell Biol. 1989;5:483–525. doi: 10.1146/annurev.cb.05.110189.002411. [DOI] [PubMed] [Google Scholar]
  10. Kornfeld S. Trafficking of lysosomal enzymes. FASEB J. 1987 Dec;1(6):462–468. doi: 10.1096/fasebj.1.6.3315809. [DOI] [PubMed] [Google Scholar]
  11. Kotlikoff M. I., Murray R. K., Reynolds E. E. Histamine-induced calcium release and phorbol antagonism in cultured airway smooth muscle cells. Am J Physiol. 1987 Oct;253(4 Pt 1):C561–C566. doi: 10.1152/ajpcell.1987.253.4.C561. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Lew D. B., Chodimella V., Murlas C. G. Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-beta-D-glucosaminidase activity in bronchoalveolar lavage fluid. Lung. 1990;168(5):273–283. doi: 10.1007/BF02719704. [DOI] [PubMed] [Google Scholar]
  14. Lew D. B., Leslie C. C., Riches D. W., Henson P. M. Induction of macrophage lysosomal hydrolase synthesis and secretion by beta-1,3-glucan. Cell Immunol. 1986 Jul;100(2):340–350. doi: 10.1016/0008-8749(86)90034-1. [DOI] [PubMed] [Google Scholar]
  15. Li S. C., Hirabayashi Y., Li Y. T. A protein activator for the enzymic hydrolysis of GM2 ganglioside. J Biol Chem. 1981 Jun 25;256(12):6234–6240. [PubMed] [Google Scholar]
  16. Mahuran D., Lowden J. A. The subunit and polypeptide structure of hexosaminidases from human placenta. Can J Biochem. 1980 Apr;58(4):287–294. doi: 10.1139/o80-038. [DOI] [PubMed] [Google Scholar]
  17. Morgan D. O., Edman J. C., Standring D. N., Fried V. A., Smith M. C., Roth R. A., Rutter W. J. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987 Sep 24;329(6137):301–307. doi: 10.1038/329301a0. [DOI] [PubMed] [Google Scholar]
  18. Murray J. J., Tonnel A. B., Brash A. R., Roberts L. J., 2nd, Gosset P., Workman R., Capron A., Oates J. A. Release of prostaglandin D2 into human airways during acute antigen challenge. N Engl J Med. 1986 Sep 25;315(13):800–804. doi: 10.1056/NEJM198609253151304. [DOI] [PubMed] [Google Scholar]
  19. Panettieri R. A., Yadvish P. A., Kelly A. M., Rubinstein N. A., Kotlikoff M. I. Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression. Am J Physiol. 1990 Dec;259(6 Pt 1):L365–L371. doi: 10.1152/ajplung.1990.259.6.L365. [DOI] [PubMed] [Google Scholar]
  20. Stahl P. D., Rodman J. S., Miller M. J., Schlesinger P. H. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1399–1403. doi: 10.1073/pnas.75.3.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stahl P., Schlesinger P. H., Sigardson E., Rodman J. S., Lee Y. C. Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: characterization and evidence for receptor recycling. Cell. 1980 Jan;19(1):207–215. doi: 10.1016/0092-8674(80)90402-x. [DOI] [PubMed] [Google Scholar]
  22. Sung S. S., Nelson R. S., Silverstein S. C. Yeast mannans inhibit binding and phagocytosis of zymosan by mouse peritoneal macrophages. J Cell Biol. 1983 Jan;96(1):160–166. doi: 10.1083/jcb.96.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takizawa T., Thurlbeck W. M. Muscle and mucous gland size in the major bronchi of patients with chronic bronchitis, asthma, and asthmatic bronchitis. Am Rev Respir Dis. 1971 Sep;104(3):331–336. doi: 10.1164/arrd.1971.104.3.331. [DOI] [PubMed] [Google Scholar]
  24. Tonnel A. B., Joseph M., Gosset P., Fournier E., Capron A. Stimulation of alveolar macrophages in asthmatic patients after local provocation test. Lancet. 1983 Jun 25;1(8339):1406–1408. doi: 10.1016/s0140-6736(83)92356-5. [DOI] [PubMed] [Google Scholar]
  25. Vladutiu G. D., Rattazzi M. C. Excretion-reuptake route of beta-hexosaminidase in normal and I-cell disease cultured fibroblasts. J Clin Invest. 1979 Apr;63(4):595–601. doi: 10.1172/JCI109341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Waheed A., Braulke T., Junghans U., von Figura K. Mannose 6-phosphate/insulin like growth factor II receptor: the two types of ligands bind simultaneously to one receptor at different sites. Biochem Biophys Res Commun. 1988 May 16;152(3):1248–1254. doi: 10.1016/s0006-291x(88)80419-4. [DOI] [PubMed] [Google Scholar]
  27. Warr G. A. A macrophage receptor for (mannose/glucosamine)-glycoproteins of potential importance in phagocytic activity. Biochem Biophys Res Commun. 1980 Apr 14;93(3):737–745. doi: 10.1016/0006-291x(80)91139-0. [DOI] [PubMed] [Google Scholar]
  28. von Figura K., Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–193. doi: 10.1146/annurev.bi.55.070186.001123. [DOI] [PubMed] [Google Scholar]

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

RESOURCES