Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Jan;67(1):210–215. doi: 10.1172/JCI110015

Prolylcarboxypeptidase (angiotensinase C) in human lung and cultured cells.

K Kumamoto, T A Stewart, A R Johnson, E G Erdös
PMCID: PMC371589  PMID: 7451650

Abstract

The activity of prolylcarboxypeptidase (PCP), or angiotensinase C, was measured in lung tissues, leukocytes, and cultured human cells using Cbz-Pro-[14C]Ala as a substrate. A lysosomal fraction of homogenized rat or human lung contained most of the PCP activity in that tissue. Polymorphonuclear neutrophils, macrophages, and lymphocytes isolated from human blood had PCP activity. Fibroblasts cultured from human tissues had the highest activity (0.56-1.15 mumol/h per 10(6) cells), more than endothelial cells cultured from human pulmonary arteries. PCP of cultured human fibroblasts was similar to the human renal enzyme because it was resistant to moderate heating and was not inhibited by p-chloromercuriphenyl sulfonic acid. These properties and the substrate specificity distinguish PCP from cathepsin A, which is also in fibroblasts. Antibody to human renal PCP reacted with fibroblast PCP in immunofluorescence, indicating common antigenic determinants. Hydrocortisone changed PCP activity in fibroblasts in parallel with changes in beta-glucuronidase activity and cell-protein concentration; the activity was depressed at low concentration of the hormone. PCP activity was also found in synovial fluid from arthritic joints and in fibroblasts from the synovium. That PCP is found in both inflammatory exudates and in cells that appear at sites of inflammation indicates that, in addition to inactivating angiotensins, this enzyme may have a role in inflammation.

Full text

PDF
210

Images in this article

213Image
on p.213

Selected References

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

  1. Bakhle Y. S., Vane J. R. Pharmacokinetic function of the pulmonary circulation. Physiol Rev. 1974 Oct;54(4):1007–1045. doi: 10.1152/physrev.1974.54.4.1007. [DOI] [PubMed] [Google Scholar]
  2. Bowen D. M., Davison A. N. Cathepsin A in human brain and spleen. Biochem J. 1973 Feb;131(2):417–419. doi: 10.1042/bj1310417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  4. Doi E., Kawamura Y., Matoba T., Hata T. Cathepsin A of two different molecular sizes in pig kidney. J Biochem. 1974 Apr;75(4):889–894. doi: 10.1093/oxfordjournals.jbchem.a130462. [DOI] [PubMed] [Google Scholar]
  5. Doi E. Stabilization of pig kidney cathepsin A by sucrose and chloride ion, and inhibition of the enzyme activity by diisopropyl fluorophosphate and sulfhydryl reagents. J Biochem. 1974 Apr;75(4):881–887. doi: 10.1093/oxfordjournals.jbchem.a130461. [DOI] [PubMed] [Google Scholar]
  6. Gaynes R. P., Szidon J. P., Oparil S. In vivo and in vitro conversion of des-1-Asp angiotensin I to angiotensin III. Biochem Pharmacol. 1978;27(24):2871–2877. doi: 10.1016/0006-2952(78)90203-4. [DOI] [PubMed] [Google Scholar]
  7. Grove G. L., Cristofalo V. J. Characterization of the cell cycle of cultured human diploid cells: effects of aging and hydrocortisone. J Cell Physiol. 1977 Mar;90(3):415–422. doi: 10.1002/jcp.1040900305. [DOI] [PubMed] [Google Scholar]
  8. Johnson A. R., Erdös E. G. Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase. J Clin Invest. 1977 Apr;59(4):684–695. doi: 10.1172/JCI108687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson A. R. Human pulmonary endothelial cells in culture. Activities of cells from arteries and cells from veins. J Clin Invest. 1980 Apr;65(4):841–850. doi: 10.1172/JCI109736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kakimoto T., Oshima G., Yeh H. S., Erdös E. G. Purification of lysosomal prolycarboxypeptidase angiotensinase C. Biochim Biophys Acta. 1973 Mar 15;302(1):178–182. doi: 10.1016/0005-2744(73)90021-1. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Logunov A. I., Orekhovich V. N. Isolation and some properties of cathepsin A from bovine spleen. Biochem Biophys Res Commun. 1972 Feb 16;46(3):1161–1168. doi: 10.1016/s0006-291x(72)80096-2. [DOI] [PubMed] [Google Scholar]
  13. Maca R. D., Fry G. L., Hoak J. C. The effects of glucocorticoids on cultured human endothelial cells. Br J Haematol. 1978 Apr;38(4):501–509. doi: 10.1111/j.1365-2141.1978.tb01075.x. [DOI] [PubMed] [Google Scholar]
  14. Matsunaga M. Nature of lysosomal angiotensinase activity. Jpn Circ J. 1971 Mar;35(3):333–338. doi: 10.1253/jcj.35.333. [DOI] [PubMed] [Google Scholar]
  15. McDonald J. K., Zeitman B. B., Callahan P. X., Ellis S. Angiotensinase activity of dipeptidyl aminopeptidase I (cathepsin C) of rat liver. J Biol Chem. 1974 Jan 10;249(1):234–240. [PubMed] [Google Scholar]
  16. McDonald J. K., Zeitman B. B., Ellis S. Detection of a lysosomal carboxypeptidase and a lysosomal dipeptidase in highly-purified dipeptidyl aminopeptidase I (cathepsin C) and the elimination of their activities from preparations used to sequence peptides. Biochem Biophys Res Commun. 1972 Jan 14;46(1):62–70. doi: 10.1016/0006-291x(72)90630-4. [DOI] [PubMed] [Google Scholar]
  17. Odya C. E., Marinkovic D. V., Hammon K. J., Stewart T. A., Erdös E. G. Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney. J Biol Chem. 1978 Sep 10;253(17):5927–5931. [PubMed] [Google Scholar]
  18. Rosenberg S. A., Lipsky P. E. Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol. 1979 Mar;122(3):926–931. [PubMed] [Google Scholar]
  19. Smith B. T., Giroud C. J. Effects of cortisol on serially propogated fibroblast cell cultures derived from the rabbit retal lung and skin. Can J Physiol Pharmacol. 1975 Dec;53(6):1037–1041. doi: 10.1139/y75-144. [DOI] [PubMed] [Google Scholar]
  20. Taylor H. A., Thomas G. H., Miller C. S., Kelly T. E., Siggers D. Mucolipidosis 3 (pseudo-Hurler polydystrophy): cytological and ultrastructural observations of cultured fibroblast cells. Clin Genet. 1973;4(5):388–397. doi: 10.1111/j.1399-0004.1973.tb01165.x. [DOI] [PubMed] [Google Scholar]
  21. Yang H. Y., Erdös E. G., Chiang T. S. New enzymatic route for the inactivation of angiotensin. Nature. 1968 Jun 29;218(5148):1224–1226. doi: 10.1038/2181224a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES