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Phenotypic Markers of Alveolar Macrophage Maturation in Pulmonary Sarcoidosis

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Abstract

The expression of maturation-associated antigens on alveolar mac-rophages (AMs) was studied in bronchoalveolar fluid of 30 patients with sarcoidosis and 11 control subjects. The percent of AMs expressing CD14 or CDllb (common for blood monocytes) was significantly increased in patients with active sarcoidosis compared to those with inactive disease, and control subjects. On the other hand, the mean expression of antigens characteristic for mature macrophages showed no significant difference (25F9), or was even increased in patients with sarcoidosis (CD71, KiM8). Since CD14 and CDllb molecules were also frequently expressed on large phagocytes morphologically similar to mature macrophages, and recent stud-ies showed modulation of these glycoproteins by the activation of myeloid cells, our data indicate that the majority of AMs recovered by bronchoal-veolar lavage in sarcoidosis are mature, activated cells.

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References

  1. Agostini C, Semenzato G (1990) Immune responses in the lung: basic principles. Lung 168 (Suppl): 1001–1012

    Article  PubMed  Google Scholar 

  2. Agostini C, Garbisa S, Trentin L, Zambello R, Fastelli G, Onisto M, Cipriani A, Festi G, Casara D, Semenzato G (1989) Pulmonary alveolar macrophages from patients with active sarcoidosis express Type IV collagenolytic proteinase. An enzymatic mechanism for influx of mononuclear phagocytes at sites of disease activity. J Clin Invest 84:605–612

    Article  PubMed  CAS  Google Scholar 

  3. Ainslie GM, Poulter LW, Du Bois RM (1989) Relation between immunocytological features of bronchoalveolar lavage fluid and clinical indices in sarcoidosis. Thorax 44:501–509

    Article  PubMed  CAS  Google Scholar 

  4. Andreesen R, Osterholz J, Bodemann H, Bross KJ, Costabel U, Lohr GW (1984) Expression of transferrin receptors and intracellular ferritin during terminal differentiation of human monocytes. Blut 49:195–202

    Article  PubMed  CAS  Google Scholar 

  5. Barth J, Kreipe H, Kiemle-Kallee J, Radzun H, Parwaresch MR, Petermann W (1988) Diminished activity of tartarate resistant acid phosphatase in alveolar macrophages from patients with active sarcoidosis. Thorax 43:901–904

    Article  PubMed  CAS  Google Scholar 

  6. Barth J, Petermann W, Entzian P, Kreipe H, Radzun HJ, Parwaresch MR (1988) Characterization of alveolar macrophages from sarcoidosis patients using different monoclonal antibodies of the Ki-series. In: Grassi C, Rizzato G, Pozzi E (eds) Sarcoidosis and other granulomatous disorders. Elsevier, Amsterdam, pp 183–184

    Google Scholar 

  7. Bazil V, Strominger JL (1991) Shedding as a mechanism of down-modulation of CD 14 on stimulated human monocytes. J Immunol 147:1567–1574

    PubMed  CAS  Google Scholar 

  8. Calhoun WJ, Salisbury SM (1989) Heterogeneity in cell recovery and superoxide production in buoyant, density-defined subpopulations of human alveolar macrophages from healthy volunteers and sarcoidosis patients. J Lab Clin Med 114:682–690

    PubMed  CAS  Google Scholar 

  9. Costabel U, Bross KJ, Matthys H (1985) A new method for the demonstration of surface antigens on bronchoalveolar lavage cells. Bull Eur Physiopathol Respir 21:381–387

    PubMed  CAS  Google Scholar 

  10. Costabel U, Zaiss A, Wagner DJ, Baur R, Rühle KH, Matthys H (1988) Value of bronchoal-veolar lavage lymphocyte subpopulations for the diagnosis of sarcoidosis. In: Grassi C, Rizzato C, Pozzi E (eds) Sarcoidosis and other granulomatous disorders. Elsevier, Amsterdam, pp 429–432

    Google Scholar 

  11. Costabel U, Andreesen R, Bross KJ, Kroegel C, Teschler H, Walter M (1989) Role of cells and mediators for granuloma formation in pulmonary sarcoidosis. In: Yoshida T, Torisu M (eds) Basic mechanisms of granulomatous formation. Elsevier, Amsterdam, pp 319–343

    Google Scholar 

  12. Crystal RG (1991) Alveolar macrophages. In: Crystal RG, West JB (eds) The lung: scientific foundations. Raven Press, New York, pp 527–538

    Google Scholar 

  13. Danel C, Dewar A, Turner-Warwick M, Chretien J (1983) Ultrastructural changes in bronchoalveolar lavage cells in sarcoidosis and comparison with the tissue granuloma. Am J Pathol 112:7–17

    PubMed  CAS  Google Scholar 

  14. Gant VA, Shakoor Y, Barbosa IL, Hamblin AS (1991) Normal and sarcoid alveolar macrophages differ in their ability to present antigen and to cluster with autologous lymphocytes. Clin Exp Immunol 86:494–499

    Article  PubMed  CAS  Google Scholar 

  15. Hance AJ, Douches S, Winchester RJ, Ferrans VJ, Crystal RG (1985) Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis. J Immunol 134:284–292

    PubMed  CAS  Google Scholar 

  16. Haslam PL, Parker DJ, Townsed PJ (1990) Increases in HLA-DQ, DP, DR, and transferrin receptors on alveolar macrophages in sarcoidosis and allergic alveolitis compared with fibrosing alveolitis. Chest 97:651–661

    Article  PubMed  CAS  Google Scholar 

  17. Hirata T, Bitterman PB, Mornex JF, Crystal RG (1986) Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation. J Immunol 136:1339–1345

    PubMed  CAS  Google Scholar 

  18. Hoogsteden HC, van Dongen JJM, van Hal PTW, Delahaye M, Hop W, Hilvering Ch (1989) Phenotype of blood monocytes and alveolar macrophages in interstitial lung disease. Chest 95:574–577

    Article  PubMed  CAS  Google Scholar 

  19. Ina Y, Takada K, Yamamoto M, Morishita M, Miyachi A (1990) Antigen presenting capacity in patients with sarcoidosis. Chest 98:911–916

    Article  PubMed  CAS  Google Scholar 

  20. Klech H, Neuchrist C, Pohl W, Schenk E, Sorg C, Knapp W, Luger TH, Scheiner O, Kraft D (1988) Phenotyping of alveolar macrophage subpopulations in pulmonary sarcoidosis. Relation to intracellularinterleukin-1 production. In: Grassi C, Rizzato G, Pozzi E (eds) Sarcoidosis and other granulomatous disorders. Elsevier, Amsterdam, pp 115–122

    Google Scholar 

  21. Kunkel SL, Chensue SW, Strieter RM, Lynch JP, Remich DG (1989) Cellular and molecular aspects of granulomatous inflammation. Am J Respir Cell Mol Biol 1:439–447

    PubMed  CAS  Google Scholar 

  22. Landmann R, Wesp M, Obrecht JP (1991) Cytokine regulation of the myeloid glycoprotein CD14. Pathobiology 59:131–135

    Article  PubMed  CAS  Google Scholar 

  23. Lern VM, Lipscomb MF, Weissler JC, Nunez G, Ball EJ, Stastny P, Toews GB (1985) Bronchoalveolar cells from sarcoid patients demonstrate enhanced antigen presentation. J Immunol 135:1766–1771

    Google Scholar 

  24. Lund-Johansen F, Olweus J, Aarli A, Bjerknes R (1990) Signal transduction in human monocytes and granulocytes through the Pi-linked antigen CD14. FEBS Lett 273:55–58

    Article  PubMed  CAS  Google Scholar 

  25. Lundahl J, Halldén G, Hed J, Johansson SGO (1991) A flow cytometric method to measure the stimulated mobilization and the intracellular pool of the adhesion promoting glucoprotein Mac-1. APMIS 99:139–146

    Article  PubMed  CAS  Google Scholar 

  26. Mathison J, Tobias P, Wolfson E, Ulevitch R (1991) Regulatory mechanisms of host responsiveness to endotoxin (lipopolysaccharide). Pathobiology 59:185–188

    Article  PubMed  CAS  Google Scholar 

  27. Melis M., Gjomarkaj M, Pace E, Malizia G, Spatafora M (1991) Increased expression of leukocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) by alveolar macrophages of patients with pulmonary sarcoidosis. Chest 100:910–916

    Article  PubMed  CAS  Google Scholar 

  28. Meyer KC, Kaminski MJ, Calhoun WJ, Auerbach R (1989) Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. I. Enhanced capacity of bronchoalveolar lavage cells from patients with pulmonary sarcoidosis to induce angiogenesis in vivo. Am Rev Respir Dis 140:1446–1449

    PubMed  CAS  Google Scholar 

  29. Moseley PL, Hemken Ch, Monick M, Nugent K, Hunninghake GW (1986) Interferon and growth factor activity for human lung fibroblasts. Release from bronchoalveolar cells from patients with active sarcoidosis. Chest 89:657–662

    Article  PubMed  CAS  Google Scholar 

  30. Mues B, von Eiff M, Koestering A, van de Loo J, Sorg C (1989) Heterogeneity of alveolar macrophages in acute and chronic inflammatory lung diseases. Eur Respir J 2:699s.

    Google Scholar 

  31. Nakstad B, Lyberg T, Skjorten F, Boye NP (1989) Antigenic specificity of human alveolar macrophages and blood monocytes studied by an immunofluorescence technique. J Pathol 157:99–107

    Article  PubMed  CAS  Google Scholar 

  32. Noble B, Dubois RM, Poulter LW (1989) The distribution of phenotypically distinct macrophage subsets in the lungs of patients with cryptogenic fibrosing alveolitis. Clin Exp Immunol 76:41–46

    PubMed  CAS  Google Scholar 

  33. Peters JH, Ruppert J, Gieseler RKH, Najar HM, Xu H (1991) Differentiation of human monocytes into CD 14 negative accessory cells: do dendritic cells derive from the monocytic lineage? Pathobiology 59:122–126

    Article  PubMed  CAS  Google Scholar 

  34. Pulford K, Micklem K, McCarthy S, Cordell J, Jones M, Mason DY (1992) A monocyte/ macrophage antigen recognized by the four antibodies GHI/61, Ber-MAC3, Ki-M8, and SM4. Immunology 75:588–595

    PubMed  CAS  Google Scholar 

  35. Radzun HJ, Kreipe H, Bodewadt S, Hansmann ML, Barth J, Parwaresch MR (1987) Ki-M8 monoclonal antibody reactive with an intracytoplasmic antigen on monocyte/macrophage lineage. Blood 69:1320–1327

    PubMed  CAS  Google Scholar 

  36. Rennard SI, Bitterman PB, Crystal RG (1984) Mechanisms of fibrosis. Am Rev Respir Dis 130:492–496

    CAS  Google Scholar 

  37. Robinson PJ (1991) Phosphatidylinositol membrane anchors and T-cell activation. Immunol Today 12:35–41

    Article  PubMed  CAS  Google Scholar 

  38. Sibille Y, Reynolds HY (1990) Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 141:474–501

    Google Scholar 

  39. Sibille Y, Houssiau F, Pochet JM, Staquet P, van Snick J, van Leuven F (1990) Alpha-2-macroglobulin and interleukin-6 (IL-6) release by human alveolar macrophages from normals and sarcoidosis patients. Am Rev Respir Dis 141:A871

    Google Scholar 

  40. Sone S, Okubo A, Ogura T (1989) Normal human alveolar macrophages have more ability than blood monocytes to produce cell-associated interleukin-1-alpha. Am J Respir Cell Mol Biol 1:507–515

    PubMed  CAS  Google Scholar 

  41. Sorg C. (1991) Macrophages in acute and chronic inflammation. Chest 100 (Suppl)3:173S-175S

    PubMed  CAS  Google Scholar 

  42. Spatafora M, Merendino A, Chiappara G, Gjomarkaj M, Melis M, Bellia V, Bonsignore G (1989) Lung compartmentalization of increased TNF releasing ability by mononuclear phagocytes in pulmonary sarcoidosis. Chest 96:542–549

    Article  PubMed  CAS  Google Scholar 

  43. Spiteri MA, Clarke SW, Poulter LW (1992) Alveolar macrophages that suppress T-cell responses may be crucial to the pathogenetic outcome of pulmonary sarcoidosis. Eur Respir J 5:394–403

    PubMed  CAS  Google Scholar 

  44. Striz I, Wang YM, Kalaycioglu O, Costabel U (1992) Expression of alveolar macrophage adhesion molecules in pulmonary sarcoidosis. Chest 102:882–886

    Article  PubMed  CAS  Google Scholar 

  45. Venet A, Hance AJ, Saltini C, Robinson BWS (1985) Enhanced alveolar macrophage-mediated antigen-induced T-lymphocyte proliferation in sarcoidosis. J Clin Invest 75:1488–1495

    Article  Google Scholar 

  46. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431–1433

    Article  PubMed  CAS  Google Scholar 

  47. Ziegler-Heitbrock HWL, Ströbel M, Fingerle G, Schlunck T, Pforte A, Blumenstein M, Haas JG (1991) Small (CD14+/CD16+) monocytes and regular monocytes in human blood. Pathobi-ology 59:127–130

    Article  CAS  Google Scholar 

  48. Zwadlo G, Bröcker EB, von Bassewitz DB, Feige U, Sorg C (1985) A monoclonal antibody to a differentiation antigen present on mature human macrophages and absent from monocytes. J Immunol 134:512–518

    Google Scholar 

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Stîíž, I., Wang, Y.M., Teschler, H. et al. Phenotypic Markers of Alveolar Macrophage Maturation in Pulmonary Sarcoidosis. Lung 171, 293–303 (1993). https://doi.org/10.1007/BF03215872

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