Skip to main content
PMC home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2004 Jun 17;130(6):603–614. doi: 10.1016/S0022-2143(97)90110-4

Peptidases in human bronchoalveolar lining fluid, macrophages, and epithelial cells: Dipeptidyl (amino)peptidase IV, aminopeptidase N, and dipeptidyl (carboxy)peptidase (angiotensin-converting enzyme)☆

Lucienne Juillerat-Jeanneret a,b,∗, John-david Aubert a,b, Philippe Leuenberger a,b
PMCID: PMC7131187  PMID: 9422334

Abstract

The modulation of proteolytic activity is an important factor in regulating the metabolism and function of peptide hormones. In this study, the activities of dipeptidyl (carboxy)peptidase (angiotensin-converting enzyme (ACE)), aminopeptidase N (APN), and dipeptidyl (amino)peptidase IV (DPP IV) were measured in the blood, the human bronchial epithelial and alveolar cells, bronchoalveolar macrophages, and the soluble phase of bronchoalveolar lavage (BAL) samples obtained from normal human volunteers and patients with pulmonary pathologic conditions. BAL fluid expressed ACE activity and very low levels of APN and DPP IV activities in the volunteer population, but higher levels could be measured in samples from patients. In patients, increased APN corresponded to a high granulocyte count, while DPP IV and ACE were associated with a high percentage of lymphocytes. Neither AIDS nor smoking induced an increased level of these enzymes. Immunohistochemical staining of bronchoalveolar smears with anti-human ACE monoclonal antibody showed that only macrophages expressed this enzyme. Enzyme histochemistry for DPP IV and APN showed that all leukocytes expressed these activities. APN, DPP IV, and ACE activities were also found in cell extracts of bronchoalveolar macrophages. In extracts of bronchial epithelial and alveolar cells, only APN and DPP IV activities were detected. Kinetic properties of the soluble enzymes in lavage supernatants were comparable to those of serum enzymes. These results demonstrate that soluble forms of cellular enzymes found in BAL fluid are regulated independently of blood and that different cell types may release these enzymes.

Abbreviations: ACE, angiotensin-converting enzyme; AIDS, acquired immunodeficiency syndrome; APN, cminopeptidase N; BAL, bronchoalveolar lavage; DPP IV, dipeptidyl (amino)peptidose IV; γGTP, γ-glutamyltranspeptidase; HIV, human immunodeficiency virus; IC50, 50% inhibitory concentration; KM, Michaelis-Menten constant; PBS, phosphate-buffered saline solution; Z-, benzyloxycarbonyl-

Footnotes

☆

Supported by the Fund for Pulmonary Research; by grants from the Roche Research Foundation, Switzerland; by the Swiss Public Health Office (AIDS Fund, Grant 3139-041861.94); and by the Swiss National Foundation for Scientific Research (Grant 32-39320.93).

References

  • 1.Kenny AJ, O'Hare MJ, Gusterson BA. Cell-surface peptidases as modulators of growth and differentiation. Lancet. 1989;2:785–787. doi: 10.1016/s0140-6736(89)90841-6. [DOI] [PubMed] [Google Scholar]
  • 2.Kenny AJ, Bourne A. Cellular reorganisation of membrane peptidases in Wallerian degeneration of pig peripheral nerve. J Neurocytol. 1991;20:875–885. doi: 10.1007/BF01190466. [DOI] [PubMed] [Google Scholar]
  • 3.Cooper PH, Mayer P, Baggiolini M. Stimulation of phagocytosis in bone-marrow derived mouse macrophages by bacterial lipopolysaccharide: correlation with biochemical and functional parameters. J Immunol. 1984;133:913–922. [PubMed] [Google Scholar]
  • 4.Koito A, Hattori T, Murakami S. A neutralizing epitope of human deficiency virus type 1 has homologous aminoacid sequence with the active site of inter-α-trypsin inhibitor. Int Immunol. 1989;1:613–618. doi: 10.1093/intimm/1.6.613. [DOI] [PubMed] [Google Scholar]
  • 5.O'Brien RF, Cohn DL. Serum angiotensin converting enzyme levels in AIDS. Chest. 1990;97:1021–1022. doi: 10.1378/chest.97.4.1021b. [DOI] [PubMed] [Google Scholar]
  • 6.Kozlovski S, Corr M, Takeshita T. Serum angiotensin-I converting enzyme activity processes a human immunodeficiency virus-1 gp160 peptide for presentation by major histocompatibility complex class I molecules. J Exp Med. 1992;175:1417–1422. doi: 10.1084/jem.175.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Luisetti M, Piccioni PD, Donnetta AM, Bulgheroni A, Peona V. Protease-antiprotease imbalance: local evaluation with bronchoalveolar lavage. Respiration. 1992;59:24–27. doi: 10.1159/000196099. [DOI] [PubMed] [Google Scholar]
  • 8.Reddel RR, Ke Y, Gerwin BI. Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transformation via strontium phosphate coprecipitation with a plasmid containing SV40 early region gene. Cancer Res. 1988;48:1904–1909. [PubMed] [Google Scholar]
  • 9.Klech H, Pohl W. Technical recommendations and guidelines for bronchoalveolar lavages (BAL) Eur Resp J. 1989;2:561–585. [PubMed] [Google Scholar]
  • 10.Juillerat-Jeanneret L, Aguzzi A, Wiestler OD, Darekar P, Janzer RC. Dexamethasone selectively regulates the activity of enzymatic markers of cerebral endothelial cell lines. In Vitro Cell Dev Biol. 1992;28A:537–543. doi: 10.1007/BF02634138. [DOI] [PubMed] [Google Scholar]
  • 11.Juillerat-Jeanneret L. Modulation of proteolytic activity in tissues following chronic inhibition of angiotensin-converting enzyme. Biochem Pharmacol. 1993;45:1447–1454. doi: 10.1016/0006-2952(93)90044-w. [DOI] [PubMed] [Google Scholar]
  • 12.Juillerat L, Nussberger Y, Ménard J, Mooser V, Christen Y, Waeber B. Determinants of angiotensin II generation during converting enzyme inhibition. Hypertension. 1990;16:564–572. doi: 10.1161/01.hyp.16.5.564. [DOI] [PubMed] [Google Scholar]
  • 13.Danilov SM, Jaspard E, Churakova T. Structure-function analysis of angiotensin I—converting enzyme using monoclonal antibodies. J Biol Chem. 1994;269:26806–26814. [PubMed] [Google Scholar]
  • 14.Schullek JR, Wilson IB. Angiotensin converting enzyme: substrate inhibition. Peptides. 1989;10:431–434. doi: 10.1016/0196-9781(89)90054-5. [DOI] [PubMed] [Google Scholar]
  • 15.Weisser K, Scloos J. Measurement of serum ACE activity in vitro after administration of enalapril in man cannot reflect inhibition of the enzyme in vivo. Methods Find Exp Clin Pharmacol. 1993;15:413–418. [PubMed] [Google Scholar]
  • 16.Dragovic T, Igic R, Erdös EG, Rabito SF. Metabolism of bradykinin by peptidases in the lung. Am Rev Respir Dis. 1993;147:1491–1496. doi: 10.1164/ajrccm/147.6_Pt_1.1491. [DOI] [PubMed] [Google Scholar]
  • 17.Specks U, Martin WJ, Rohrbach MS. Bronchoalveolar lavage fluid angiotensin-converting enzyme in interstitial lung diseases. Am Rev Respir Dis. 1990;141:117–123. doi: 10.1164/ajrccm/141.1.117. [DOI] [PubMed] [Google Scholar]
  • 18.Lindgren BR, Andersson RGG. Angiotensin-converting enzyme inhibitors and their influence on inflammation, bronchial reactivity and cough. Med Toxicol Adverse Drug Exp. 1989;4:369–380. doi: 10.1007/BF03259918. [DOI] [PubMed] [Google Scholar]
  • 19.Lieberman J. Elevation of serum angiotensin-converting enzyme (ACE) in sarcoidosis. Am J Med. 1975;59:365–372. doi: 10.1016/0002-9343(75)90395-2. [DOI] [PubMed] [Google Scholar]
  • 20.Bénéteau-Burnat B, Baudin B. Angiotensin-converting enzyme: clinical applications and laboratory investigations on serum and other biological fluids. Crit Rev Clin Lab Sci. 1991;28:337–356. doi: 10.3109/10408369109106868. [DOI] [PubMed] [Google Scholar]
  • 21.Deremee RA, Rohrbach MS. Serum angiotensin converting enzyme activity in evaluating the clinical course of sarcoidosis. Ann Intern Med. 1990;92:361–365. doi: 10.7326/0003-4819-92-3-361. [DOI] [PubMed] [Google Scholar]
  • 22.Allen RK, Pierce RJ, Barter CE. Angiotensin converting enzyme in bronchoalveolar lavage fluid in sarcoidosis. Sarcoidosis. 1992;9:54–59. [PubMed] [Google Scholar]
  • 23.Gorrell MD, Wickson J, McCaughan GW. Expression of the rat CD26 antigen (dipeptidyl peptidase IV) on sub-populations of rat lymphocytes. Cell Immunol. 1991;134:205–215. doi: 10.1016/0008-8749(91)90343-a. [DOI] [PubMed] [Google Scholar]
  • 24.Laouar A, Bauvois B. Characterization and modulation of cell surface proteases of human myeloblastoid (HL-60) cells and comparison to normal myeloid cells. Immunol Lett. 1992;34:257–265. doi: 10.1016/0165-2478(92)90222-a. [DOI] [PubMed] [Google Scholar]
  • 25.Jackman HL, Tan F, Schraufnagel D, Dragovie T, Dezsö B, Becker RP, Erdös EG. Plasma membrane-bound and lysosomal peptidases in human alveolar macrophages. Am J Respir Cell Mol Biol. 1995;13:196–204. doi: 10.1165/ajrcmb.13.2.7626287. [DOI] [PubMed] [Google Scholar]
  • 26.Proud D, Subauste C, Ward P. Glucocorticoids do not alter peptidase expression on an human bronchial cell line. Am J Respir Cell Mol Biol. 1994;11:57–65. doi: 10.1165/ajrcmb.11.1.7517143. [DOI] [PubMed] [Google Scholar]
  • 27.Vanham G, Kestens L, De Meester I. Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects. J AIDS. 1993;6:749–757. [PubMed] [Google Scholar]
  • 28.Saiki I, Fuji H, Yoneda J. Role of aminopeptidase N (CD13) in tumor-cell invasion and extracellular matrix degradation. Int J Cancer. 1993;54:137–143. doi: 10.1002/ijc.2910540122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Hoogsteden HC, van Hal PT, Wijkhuijs JM, Hop W, Hilvering C. Differences in expression of monocyte/macrophage surface antigens in peripheral blood and bronchoalveolar cells in interstitial lung diseases. Lung. 1993;171:149–160. doi: 10.1007/BF00183944. [DOI] [PubMed] [Google Scholar]
  • 30.Rohrbach MS, Conrad AK. Comparison of the T lymphocyte-dependent induction of angiotensin converting enzyme and leucine aminopeptidase in cultured monocytes. Clin Exp Immunol. 1991;83:510–515. doi: 10.1111/j.1365-2249.1991.tb05670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Soderberg C, Larsson S, Bergstedt-Lindqvist S, Muller E. Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection. J Virol. 1993;67:3166–3175. doi: 10.1128/jvi.67.6.3166-3175.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Delmas B, Gelfi J, L'Haridon R. Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEV. Nature. 1992;357:417–420. doi: 10.1038/357417a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Yeager CL, Ashmum RA, Williams R. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992;357:420–422. doi: 10.1038/357420a0. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Laboratory and Clinical Medicine are provided here courtesy of Elsevier

RESOURCES