Summary
In experimental tubulo-interstitial (anti-basement membrane) nephritis of the rat, granulomatous inflammation develops around immunologically altered tubular basement membranes. The present light-and electron microscopic studies indicate that in the course of the granulomatous reaction, tissue monocytes evolve from blood monocytes and pursue two independent pathways of differentation. On the one hand they may differentiate into macrophages (“distant from tubules”) or, alternatively, into epitheloid cells (“adjacent to tubules”). The latter, through cell fusion, develop into multinucleated giant cells of the Langhans’ type. The cytoplasmic components of the epitheloid cells and the multinucleated giant cells should be interpreted as an activation of cellular biosynthesis. Its products, upon being secreted at the immunodefective basement membrane, will obviously serve immune defense mechanisms.
Zusammenfassung
Im Verlaufe der experimentellen tubulo-interstitiellen Nephritis (vom Typ der Antibasalmembrannephritis) der Ratte entwickelt sich um die immunalterierten tubulären Basalmembranen der Rinde eine granulomatöse Entzündung. Die Beteiligung der Monocyten und ihre weitere Differenzierung im Verlaufe des Prozesses wird in Abhängigkeit von der jeweiligen Lokalisation zum Immunort licht-und elektronenmikroskopisch verfolgt: aus den Blutmonocyten gehen die Gewebsmonocyten hervor, die sich einerseits zu Makrophagen („tubulusfern“), andererseits und unabhängig davon zu Epitheloidzellen („tubulusnah“) transformieren. Aus letzteren entstehen durch Verschmelzung die mehrkernigen Riesenzellen vom Langhans-Typ. Die Ausstattung der Epitheloidzellen und erst recht die der Riesenzellen läßt auf eine hohe Aktivierung synthetisierender Prozesse schließen ; diese führt zur Bildung von vesiculären und granulären Elementen, deren Ausschleusung am Immunort nahegelegt wird.
Similar content being viewed by others
References
Adams DO (1974) The structure of mononuclear phagocytes differating in vivo. I. Sequential fine and histologic studies of bacillus Calmette Guerin (BCG). Am J Pathol 76:17–48
Adams DO (1976) The granulomaous inflammatory response. Am J Pathol 84:164–191
Andres GA, Szymanski C, Albini B, Brentjens J, Milgrom M, Noble B, Ossi E, Steblay RW (1979) Structural observations on epitheloid and giant cells in experimental autoimmune tubulointerstitial nephritis in guinea pigs. Am J Pathol 96:21–34
Axline SG (1970) Functional biochemistry of macrophage. Semin Hematol 7:142–160
Black MM, Epstein WL (1974) Formation of multinucleate giant cells in organized epitheloid cell granulomas. Am J Pathol 74:263–274
Bönicke R, Fasske E, Themann H (1963) Submikroskopische und enzymhistochemische Beiträge zur formalen Genese des Epitheloidzellgranuloms. Klin Wochenschr 41:753–768
Browett PJ, Simpson LO, Blennerhassett JB (1979) Experimental granulomatous inflammation: The ultrastructure of the granuloma induced by injection of tubercle bacilli into Freund adjuvantsensitised guinea-pigs. J Pathol 129:191–201
Cain H, Kraus B (1980) Mehrkernige Riesenzellen in Granulomen. Virchows Arch [Pathol Anat] 385:309–333
Carr J (1980) Saŕcoid macrophage giant cells. Virchows Arch [Cell Pathol] 32:147–155
Chambers TJ (1977) Fusion of macrophages following simultaneous attempted phagocytosis of glutaraldehyd-fixed red cells. J Pathol 122:71–80
Cohn ZA, Hirsch, JG, Fedorko ME (1966) The in vitro differentiation of mononuclear phagocytes. IV. The ultrastructure of macrophage differentation in the peritoneal cavity and in the culture. J Exp Med 123:747–756
Cohn ZA (1968) The structure and function of monocytes and macrophages. Adv Immunol 9:163–214
Dannenberg AM Jr (1968) Cellular hypersensitivity and cellular immunity in the pathogenesis of tuberculosis: Specificity, systemic and local nature, and associated macrophage enzymes. Bacteriol Rev 32:85–102
Elias PM, Epstein WL (1968) Ultrastructural observations on experimentaly induced foreign-body and organized epitheloid cells granulomas in man. Am J Pathol 52:1207–1223
Epstein WL, Krasnobrod H (1968) The origin of epitheloid cells in experimental granulomas in man. Lab Invest 18:190–195
Fedorko ME, Hirsch JG (1970) Structure of monocytes and macrophages. Semin Hematol 7:109–124
Furth R van (1970) Origin and kinetics of monocytes and macrophages. Semin Hematol 7:125–141
Gusek W (1959) Über die Ultrastruktur und Natur der Epitheloidzellen. Frankf Z Pathol 69:685–694
Gusek W (1962) Submikroskopische Untersuchungen zur Feinstruktur aktiver Bindegewebszellen. Veröff Pathol 64:
James EMV, Jones-Williams W (1974) Fine structure and histochemistry of epitheloid cells in sarcoidosis. Thorax 29:115–120
Jones-Williams W, James EMV, Erasmus DA, Davies T (1970) The fine structure of sarcoid and tuberculous granulomas. Postgrad Med J 46:496–500
Judd PA, Finnegan P, Curran RC (1975) Pulmonary sarcoidosis: A clinico-pathological study. J Pathol 115:191–198
Krieger A (1979) Experimentelle autoimmune tubulointerstitielle Nephritis. Inaug Diss, München
Langer KH (1975) Niereninterstitium-Feinstrukturen und Kapillarpermeabilität. I. Feinstrukturen der zellulären und extrazellulären Komponenten des peritubulären Niereninterstitiums. Cytobiologie 10:161–184
Langer KH, Pflumm H, Müller M (1980) Zur Genese und Feinstruktur renaler (glomerulärer und peritubulärer) Riesenzellen beim Menschen und im Experiment. Verh Dt Ges Pathol 64:328–335
Leder L.-D, Crespin S (1964) Fermenthistochemische Untersuchungen zur Genese der Hautfenstermakrophagen. Frankfurter Z Pathol 73:611–628
Leder LD (1967) Der Blutmonocyt In: Experimentelle Medizin, Pathologie u. Klinik, Bd 23, Springer, Berlin-Heidelberg-New York
Lehman DH, Wilson CB, Dixon FJ (1974a) Interstitial nephritis in rats immunized with heterologous tubular basement membrane. Kidney Int 5:187–195
Lehman DH, Marquardt H, Wilson CB, Dixon FJ (1974b) Specificity of autoantibodies to tubular and glomerular basement membranes induced in guinea pigs. J Immunol 112:241–248
Mariano M, Spector WG (1974) The formation and properties of macrophage polycaryons (inflammatory giant cells). J Pathol 113:1–19
Papadimitriou JM, Spector WG (1971) The origin, fate and properties of epitheloid cells. J Pathol 105:187–203
Papadimitriou JM, Robertson TA (1980) Exocytosis by macrophage polykarion: An ultrastructural study. J Pathol 130:75–81
Pielsticker K, Krieger A, Thoenes GH (1979) Autoimmune interstitielle Nephritis: Immunhistologisch-histologische Verlaufsuntersuchungen im Tierexperiment. Verh Dt Ges Pathol 63:694
Pflumm H, Langer KH, Krieger A, Thoenes GH, Thoenes W (1980) Typen der Nierenläsion bei experimenteller (anti-TBM) interstitieller Nephritis. Elektronenmikroskopische Untersuchungen. Verh Dt Ges Pathol 64:322–327
Rebuck JW, Logrippo GA (1961) Characteristics and interrelationships of the various cells in the RE cell, macrophage, lymphocyte, and plasma cell series in man. Lab Invest 10:1068–1093
Rhee HJ van der, Burgh-de Winter CPM van der, Daems WT (1979a) The differentiation of monocytes into macrophages, epitheloid cells, and multinucleated giant cells in subcutaneous granulomas. I. Fine structure. Cell Tissue Res 197:355–378
Rhee HJ van der, Burgh-de Winter CPM van der, Daems WT (1979b) The differentation of monocytes into macrophages, epitheloid cells, and multinucleated giant cells in subcutaneous granulomas. II. Peroxidatic activity. Cell Tissue Res 197:379–396
Shima K, Dannenberg AM Jr, Ando M, Chandrasekhar S, Selizicki JA, Fabrikant JI (1972) Macrophage accumulation, division, maturation, and digestive and microbicidal capacities in tuberculous lesions. I. Studies involving their incorporation of tritiated thymidine and their content of lysosomal enzymes and bacilli. Am J Pathol 67:159–180
Spector WG (1970) The macrophage in inflammation. Ser Haematol 3:132–144
Steblay RW, Rudofsky U (1971) Renal tubular disease and autoantibodies against tubular basement membrane induced in guinea pigs. J Immunol 107:589–594
Sugisaki T, Klassen J, Milgrom F, Andres GA, McCluskey RT (1973) Immunpathologic study of an autoimmune tubular and interstitial renal disease in Brown-Norway rats. Lab Invest 28:658–671
Sutton JS, Weiss L (1966) Transformation of monocytes in tissue culture into macrophages, epitheloid cells and multinucleated giant cells. J Cell Biol 28:303–332
Thoenes W, Langer KH (1969) Die Endocytose-Phase der Eiweißresorption im proximalen Nierentubulus. Untersuchungen am Ferritin-resorbierenden Einzeltubulus der Rattenniere. Virchows Arch Abt B Zellpath 2:361–379
Unanue ER (1976) Secretory function of mononuclear phagocytes. A review. A J Pathol 83:396–417
Volkman A (1966) The origin and turnover of mononuclear cells in peritoneal exsudates in rats. J Exp Med 124:241–254
Volkman A (1970) The origin and fate of the monocyte. Ser Haematol 3:62–92
Wanstrup J, Christensen HE (1966) Sarcoidosis. 1. Ultrastructural investigations on epitheloid cell granulomas. Acta Pathol Microbiol Scand 66:169–185
Zwieten MJ van, Bhan AK, McCluskey RT, Collins AB (1976) Studies on the pathogenesis of experimental antitubular basement membrane nephritis in the guinea pig. Am J Pathol 83:531–541
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Langer, K.H., Thoenes, W. Characterization of cells involved in the formation of granuloma. Virchows Archiv B Cell Pathol 36, 177–194 (1981). https://doi.org/10.1007/BF02912065
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02912065