Abstract
To determine the responsibility of alveolar macrophage (AM) for the increased concentration of angiotensin-converting enzyme (ACE) in bronchoalveolar fluid of patients with sarcoidosis, we cultured AM recovered by bronchoalveolar lavage of 30 subjects: 9 were normal control subjects (group C), 10 had intrathoracic localized sarcoidosis (group LS), and 11 had disseminated intrathoracic and extrathoracic sarcoidosis (group DS). Cells were cultured for 7 days and synthesis of ACE was evaluated according to the difference between final (ACEqe) and initial (ACEqi) ACE content. In groups C, LS, and DS, ACEqi were, respectively, 3.0 ± 1.7, 3.3 ± 1.9, and 4.8 ± 2.4 U/106 AM, and ACEqe were 6.2 ± 1.7, 6.7 ± 2.5, and 11.3 ± 2.8 U/106 AM. ACEqe was higher than ACEqi in all 3 groups (p < 0.01). When cycloheximide was added to the AM culture, ACEqe did not differ from ACEqi, in opposition to what was observed without cycloheximide (p < 0.002). ACEqi in group LS and DS did not differ from ACEqi in Group C, but ACEqe in Group DS was higher than in Groups C and LS (p < 0.01). We conclude that AM both from normal subjects and from subjects with sarcoidosis contain ACE, cultured AM synthesize ACE, and that a greater amount of ACE is produced when AM are obtained from patients with disseminated sarcoidosis.
Similar content being viewed by others
References
Dobuler KJ, Catravas JD, Gillis CN (1982) Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine. Am Rev Respir Dis 126:534–539
Friedland J, Setton C, Silverstein E (1977) Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture. Science 197:64–65
Friedland J, Setton C, Silverstein E (1978) Induction of angiotensin converting enzyme in human monocytes in cultures. Biochem Biophys Res Commun 83:843–849
Friedland J, Silverstein E (1976) A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 66:416–424
Gee JBL, Bodel PT, Hinman LM, Stevens CA, Matthay RA, Reynolds HY (1980) Mononuclear phagocytes in sarcoidosis: lysozyme and angiotensin I converting enzyme. In: Williams WJ, Davies BH (eds) Eight international conference on sarcoidosis and other granulomatous diseases. Alpha Omega Publishing, Cardiff, pp 417–425
Gupta RG, Sicilian L, Catchatourian R, Bekerman C, Oparil S, Szidon JP (1982) Angiotensin converting enzyme in serum and in bronchoalveolar lavage in sarcoidosis. Respiration 43:153–157
Hayes LW, Goguen CA, Ching SF, Slakey LL (1978) Angiotensin-converting enzyme: accumulation in medium from cultured endothelial cells. Biochem Biophys Res Commun 82:1147–1153
Hinman LM, Stevens C, Matthay RA, Gee JBL (1979) Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis. Science 205:202–203
Hollinger MA, Giri SN, Patwell S, Zuckerman JE, Gorin A, Parsons G (1980) Effect of acute lung injury on angiotensin converting in serum, lung lavage, and effusate. Am Rev Respir Dis 121:373–376
Krieger B, Schwartz J, Loomis W, Marsh J, Spragg R (1984) Nonspecificity of elevated angiotensin converting enzyme activity in bronchoalveolar lavage fluid from high permeability lung edema states. Am Rev Respir Dis 129:499–500
Lieberman J, Nosal A, Schlessner LA, Sastre-Foken A (1979) Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis. Am Rev Respir Dis 120:329–335
Mordelet-Dambrine MS, Stanislas-Leguern GM, Huchon GJ, Baumann FC, Marsac JH, Chrétien J (1982) Elevation of the bronchoalveolar concentration of angiotensin I converting enzyme in sarcoidosis. Am Rev Respir Dis 126:472–475
Nukima T, Matsuoka R, Takagi H, Ishii Y, Arai T, Kira S (1982) Responses of serum and lung angiotensin-converting enzyme activities in the early phase of pulmonary damage induced by oleic acid in dogs. Am Rev Respir Dis 126:1080–1086
Ody C, Junod AF (1977) Converting enzyme activity in endothelial cells isolated from pig pulmonary artery and aorta. Am J Physiol 232:C95-C98
Okabe T, Suzuki A, Ishikawa H, Yotsumoto H, Ohsawa N (1981) Cells originating from sarcoid granulomas in vitro. Am Rev Respir Dis 124:608–612
Perrin-Fayolle M, Pacheco Y, Harf R, Montagnon B, Biot N (1981) Angiotensin converting enzyme in bronchoalveolar lavage fluid in pulmonary sarcoidosis. Thorax, 34:790–792
Romer FK (1979) Angiotensin-converting enzyme in sarcoidosis. Acta Med Scan 206:27–30
Roth C, Huchon GJ, Arnoux A, Stanislas-Leguern G, Marsac JH, Chrétien J (1981) Bronchoalveolar cells in advanced pulmonary sarcoidosis. Am Rev Respir Dis 124:9–12
Ryan US, Ryan JW, Whitaker C, Chiu A (1976) Localisation of angiotensin converting enzyme (kinase II) II. Immunocytochemistry and immunofluorescence. Tissue Cell 8:125–145
Shasby DM, Shasby SS, Bowman CM, Fox RB, Harada RM, Tate RM, Repine JE (1981) Angiotensin converting enzyme concentrations in the lung lavage of normal rabbits treated with nitrogen mustard exposed to hyperoxia. Am Rev Respir Dis 124:202–203
Silverstein E, Friedland J, Lyons HA, Gourin A (1976) Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum sarcoidosis; clinical and possible pathogenic significances. Ann NY Acad Sci 278:498–513
Silverstein E, Friedland J, Lyons HA, Gourin A (1976) Markedly elevated antiotensin converting enzyme containing non necrotizing granuloma in granuloma. Proc Natl Acad Sci USA 73:2137–2141
Silverstein E, Friedland J, Setton C (1978) Angiotensin converting enzyme in macrophages and Freund’s adjuvant granuloma. Isr J Med Sci 14:314–318
Silverstein E, Friedland J, Stanek AE Jr, Smith PR, Deason DR, Lyons HA (1981) Angiotensin converting enzyme: pathogenesis of sarcoidosis. Mechanisms of angiotensin converting enzyme elevation: T-lymphocyte modulation of enzyme induction in mononuclear phagocytes; enzyme properties. In: Chrétien J, Marsac J, Saltiel JC (eds) IXth international conference on sarcoidosis and other Granulomatous disorders. Pergamon Press, Paris, pp 319–325
Silverstein E, Pertshuk LP, Friedland J (1979) Immunofluorescent localization of angiotensin converting enzyme in epithelioid and giant cells of sarcoidosis granuloma. Proc Natl Acad Sci USA 76:6646–6648
Stanislas-Leguern G, Choudat D, Arnoux A, Durieux P, Lacronique J, Baumann FC, Huchon G, Marsac J, Chrétrien J (1981) Pronostic value of angiotensin converting enzyme and elveolar lymphocytes in sarcoidosis. In: Chrétien J, Marsac J, Saltiel JC (eds) IXth international conference on sarcoidosis and other granulomatous disorders. Pergamon Press, Paris, pp 424–429
Stanislas-Leguern G, Leclerc P, Baumann FC, Mordelet-Dambrine M, Huchon GJ, Andreux JP, Marsac J, Rochemaure J, Chrétrien J (1981) Angiotensin converting enzyme in bronchoalveolar fluid and serum as indicators of spread of untreated sarcoidosis. In: Chrétien J, Marsac J, Saltiel JC (eds) IXth international conference on sarcoidosis and other granulomatous disorders. Pergamon Press, Paris, pp 356–361
Studdy P, Bird R, James DG, Sherlock S (1978) Serum angiotensin-converting enzyme (SACE) in sarcoidosis and other granulomatous disorders. Lancet 2:1331–1334
Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New-York
Zar JH (1974) Biostatistical analysis. Prentice Hall, Englewood Cliffs, NJ
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stanislas-Leguern, G., Mordelet-Dambrine, M., Dusser, D. et al. In vitro synthesis of angiotensin-converting enzyme by alveolar macrophages is increased in disseminated sarcoidosis. Lung 164, 269–277 (1986). https://doi.org/10.1007/BF02713651
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02713651