The hamster cheek pouch: an immunologically privileged site suitable to the study of granulomatous infections

Arruda, M. S. P. de; Montenegro, M. R.

doi:10.1590/S0036-46651995000400004

Abstracts

The hamster check pouch is an invagination of oral mucosa, characterized histologically as skin-like. In this paper we describe anatomical, histological and embriological features of the pouch and coment on the pouch as an immunologically privileged site since it lacks lymphatic drainage and has few Langerhans cells. We present the review from literature and our observations after inoculation in the pouch of mycobacteriae (BCG, Mycobacterium tuberculosis and Mycobacterium leprae) and a fungus (Paracoccidioides brasiliensis). Lesions in the pouch were granulomatous but smaller and long lasting; even granulomatous, the reaction was inefficient to control the proliferation of agents compared with inoculation in other sites, except for BCG. Appearance of immunity was also delayed or absent and, when it was detected, a sharp decrease in number of agents in pouch lesions was observed. These observations make the pouch an interesting site for the study of the role of immune system in infeccious diseases and in granuloma formation.

Hamster cheek pouch; Inflammatory reactions; Leprosy; Paracoccidioidomycosis; granuloma; Mycobacterium leprae

A bolsa jugal do hamster (BJH) é uma invaginação da mucosa oral, caracterizada histologicamente como semelhante a pele. Nesse estudo nós descrevemos algumas de suas características anatômicas, histológicas e embriológicas e comentamos sobre sua propriedade como local imunologicamente privilegiado, considerando a ausência de drenagem linfática e o reduzido número de células de Langerhans. Apresentamos também os resultados obtidos quando da inoculação de micobacterias (BCG, Mycobacterium tuberculosis e Mycobacterium leprae) e do fungo Paracoccidioides brasiliensis na bolsa jugal. Comparada com as lesões provocadas em outras localizações e, à exceção do BCG, as lesões induzidas na bolsa são menores e de maior duração e, mesmo quando granulomatosas, incapazes de controlar a multiplicação do agente; nos casos em que houve o desenvolvimento da resposta imune, ele se fez tardiamente e foi acompanhado pela redução do número de parasitas nas lesões. Essas observações apontam a bolsa jugal do hamster como um local de escolha para o estudo sobre a participação da resposta imune no desenvolvimento e modulação das doenças infecciosas e dos granulomas.

IMMUNOLOGY

The hamster cheek pouch: an immunologically privileged site suitable to the study of granulomatous infections

A bolsa jugal do hamster: um local imunologicamente privilegiado, apropriado para o estudo das ¡nfecções granulomatosas

M. S. P. de Arruda^I; M. R. Montenegro^II

^IUniversidade Estadual Paulista, Faculdade de Ciências, Departamento de Ciências Biológicas, Bauru, SP, Brazil

^IIUniversidade Estadual Paulista, Faculdade de Medicina de Bolucatu, Departamento de Patologia, Botucatu, SP, Brazil

^{Correspondence to} Correspondence to: Maria Sueli Parreira de Arruda Faculdade de Ciências, Departamento de Ciências Biológicas, UNESP Av. Edmundo Coube, S/N 17033-360 Bauru, SP, BRASIL FAX: 0142-304470, TELEX: 0142-312 Febu, TEL: 0142-302111

SUMMARY

The hamster check pouch is an invagination of oral mucosa, characterized histologically as skin-like. In this paper we describe anatomical, histological and embriological features of the pouch and coment on the pouch as an immunologically privileged site since it lacks lymphatic drainage and has few Langerhans cells. We present the review from literature and our observations after inoculation in the pouch of mycobacteriae (BCG, Mycobacterium tuberculosis and Mycobacterium leprae) and a fungus (Paracoccidioides brasiliensis). Lesions in the pouch were granulomatous but smaller and long lasting; even granulomatous, the reaction was inefficient to control the proliferation of agents compared with inoculation in other sites, except for BCG. Appearance of immunity was also delayed or absent and, when it was detected, a sharp decrease in number of agents in pouch lesions was observed. These observations make the pouch an interesting site for the study of the role of immune system in infeccious diseases and in granuloma formation.

Keywords: Hamster cheek pouch - development; Inflammatory reactions: Leprosy: Paracoccidioidomycosis: granuloma; Mycobacterium leprae.

RESUMO

A bolsa jugal do hamster (BJH) é uma invaginação da mucosa oral, caracterizada histologicamente como semelhante a pele. Nesse estudo nós descrevemos algumas de suas características anatômicas, histológicas e embriológicas e comentamos sobre sua propriedade como local imunologicamente privilegiado, considerando a ausência de drenagem linfática e o reduzido número de células de Langerhans. Apresentamos também os resultados obtidos quando da inoculação de micobacterias (BCG, Mycobacterium tuberculosis e Mycobacterium leprae) e do fungo Paracoccidioides brasiliensis na bolsa jugal. Comparada com as lesões provocadas em outras localizações e, à exceção do BCG, as lesões induzidas na bolsa são menores e de maior duração e, mesmo quando granulomatosas, incapazes de controlar a multiplicação do agente; nos casos em que houve o desenvolvimento da resposta imune, ele se fez tardiamente e foi acompanhado pela redução do número de parasitas nas lesões. Essas observações apontam a bolsa jugal do hamster como um local de escolha para o estudo sobre a participação da resposta imune no desenvolvimento e modulação das doenças infecciosas e dos granulomas.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 13/01/95

Aceito para publicação em 04/07/95

References

1. ADAMS, D.O. - The granulomatous inflammatory re sponse. A review. Amer. J. Path., 84: 164-191, 1976.
2. ARRUDA, M.S.P.; COELHO, K.I. & MONTENEGRO, M.R. - Experimental paracoceidioidomycosis in Syrian hamster inoculated in lhe cheek pouch. Mycopathologia (Den Haag), 128: 67-73, 1994.
3. ARRUDA, M.S.P.; FLEURY, R.N. & NOGUEIRA, M.E.S. - Inoculation of the Mycobacterium leprae into the hamster cheek pouch. Leprosy Rev., 65: 399-400, 1994.
4. ARRUDA, M.S.P. & MONTENEGRO, M.R. - Granulomatous reaction in the hamsters check pouch induced by killed Paracoccidioides brasiliensis. Braz. J. med. biol. Res., 28: 209-212, 1995.
5. BARKER, F. & BILLINGHAM, R.E. - Immunologically privileged sites. Advanc. Immunol., 25: 1-54, 1977.
6. BARKER, F. & BILLINGHAM, R.E. - The lymphatic status of hamster cheek pouch tissue in relation to its properties as a graft and as a graft site. J. exp. Med., 133: 620-639, 1971.
7. BERGSTRESSER, P.R.; FLETCHER, C.R. & STREILEIN, J.W. - Surface densities of Langerhans cells in relation to rodent epidermal sites with special immunologic properties. J. invest. Derm., 74: 77-80, 1980.
8. BIJOVSKY, A.T.; MILDER, R.V.; ABRAHAMSOHN, I.A.; SINHORINI, I.L. & MARIANO, M. - The influence of lymphatic drainage in experimental Trypanosoma cruzi infection. Acta trop. (Basel), 41: 207-214, 1984.
9. BJORK, J.; SMEDEGARD, G.; SVENSJO, E. & ARFORS, K.E. - The use of the hamster cheek pouch for intracavital microscopy studies of microvascular events. Progr. Appl. Microcirc., 6: 41-53, 1984.
10. BJORK, J. & SMEDEGARD, G. - The microvasculature of the hamster cheek pouch as a model for study acute immune-complex-induced inflammatory reactions. Int. Arch. Allergy, 74: 178-185, 1990.
11. BORIC, M.P. & ALBERTINI, R. - Atrial natriuretic peptide increases microvascular blood flow and macromolecular escape during renin infusion in hamster. Microcirc. Endoth. Lymph., 6: 67-88, 1990.
12. COELHO, K.I.R.; DeFAVERI, J.; RESKALLAH-IWASSO, M.T.; PERAÇOLI, M.T. & MOTA, N.G.S. - Paracoccidioidomicose experimental. In: DEL NEGRO, G.; LACAZ, C.S. & FIORILLO, A.M. Paracoccidioidomicose, blastomicose sul-americana. Săo Paulo, Sarvier, 1982.p. 69-84.
13. COVANT, H. & HARDY, M.H. - Stability of glandular metaplasia in hamster cheek pouch explants exposed to excess retinoids. Canad. Fed. Biol. Soc Proc., 26: 119, 1983.
14. DAVIS, M.J.; FERRER, P.N. & GORE, R.W. - Vascular anatomy and hydrostatic pressure profile in the hamster cheek pouch. Amer. J. Physiol., 250: H 291-303, 1986.
15. EPSTEIN, W.L.; FURUYAMA, K.; DANNOK, K. & KWAN-WONG, E. - Granulomatous inflammation in normal and athymic mice infected with Scliislosoma mansoni: an ultrastructural study. J. Path., 127: 207-215, 1979.
16. FRANCO.M.F.; MENDES, R.P.; MOSCARDI-BACCHI, M.; REZKALLAH-IWASSO, M.T. & MONTENEGRO, M.R.G. - Paracoccidioidomycosis. Baillicre's Clin. trop. Med. comm. Dis., 4: 185-220, 1989.
17. FULTON, G.P. & MAYNARD, F.L. - Effect of cortisone on tissue mast cells in the hamster cheek pouch. Proc. Soc. exp. Biol. (N.Y.), 84: 259-260, 1953.
18. GOLDENBERG, D.M. - Reduced lymphatic drainage from hamster cheek pouch: a proposed explanation of its immunologically privileged character. Experientia (Basel), 26: 907-908, 1970.
19. HARDY, M.H.; VRABLIC, O.E.; COVANT, H.A. & KANDARKAR, S.V. - The development of the Syrian hamster cheek pouch. Anat. Rec., 214: 273-282, 1986.
20. HASTING, R.C. - Leprosy. London, Churchill Livingstone, 1985.
21. HOFFSTEN, P.E. & DIXON, F.J. - Effect of irradiation and cyclophosphamide and anti-kill antibody formation in mice. J. Immunol., 112: 564-572, 1974.
22. KANDARKAR, S.V. & SIRSAT, S.M. - Developmental morphology of hamster cheek pouch epithelium. Folia morph. (Warszawa), 32: 345-351, 1984.
23. KAPLAN, H.J. & STREILEIN, J.W. - Do immunologically sites require a functioning spleen? Nature (Lond.), 251: 553-554, 1974.
24. KONG, Y.M.; SAVAGE, D. & KONG, L.N.L. - Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immils. J. Bact., 91: 876-883, 1966.
25. KRIPKE, M.L.; MUNN, C.G.; JEEVAN, A.; TANG, J. & BUCANA, C. - Evidence that cutaneous antigen - presenting cells migrate to regional lymph node during contact sensitization. J. Immunol., 45: 2833-2838, 1990.
26. LINDERMAN, R. & STRAULI, P. - Lymphatic vessels in the cheek pouch of the golden hamster. Transplantation, 6: 557-561, 1968.
27. MAIER, M. - The relation between allergy and immunity in leprosy. Int. J. Lcprosy, 55: 116-136, 1987.
28. MENDES-GIANNINI, M.J.; CAMARGO, M.E.; LACAZ, C.S. & FERREIRA, A.W. - Immunoenzymatic absorption test for serodiagnosis of paracoccidioidomycosis. J. clin. Microbiol., 20: 103-108, 1984.
29. MICHAL, L.M.; GIESSINGER, N. & SCHRDER, R. - Reduced thrombus formation in vivo after administration of pentoxifylline (Trentol). Thromb. Res., 56: 359-368, 1989.
30. MOCK, D. & MAIN, J.H.P. - Long-term organ culture of hamster cheek pouch. J. oral Path., 5: 237-240, 1976.
31. MOCK, D. & MAIN, J.H.P. - The effect of vitamin A on hamster cheek pouch mucosa in organ culture. J. dent. Res., 58: 635-637, 1979.
32. MYIAJI, M. & NISHIMURA, K. - Granuloma formation and killing functions of granuloma in congenitally athymic nude mice infected with Blastomyces dermatitides and Paracoccidioides brasiliensis. Mycopathologia (Den Haag), 82: 129-141, 1983.
33. OPROMOLLA, D.V.A. - Noçőes de hanseniase. Bauru, Centro de Estudos Dr. Reynaldo Quagliato, 1981.
34. RAUD, J.; DAHLEN, S.E.; SMEDEGARD, G. & HEDQVIST, P. - An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch. Acta physiol. scand., 135: 95-105, 1989.
35. RAUD, J. - Vasodilatalion and inhibition of mediator release represent two distinct mechanisms for prostaglandin modulation of acute mast cell-dependent inflammation. Brit. J. Pharmacol., 99: 449-454, 1990.
36. ROBINSON, M.E.; GIBBINS, A.M. & HARDY, M.H. - Persistence of retinoids in organ culture media during induction of mucous metaplasia and glandular morphogenesis in hamster cheek pouches. Experientia (Basel), 15: 513-517, 1990.
37. ROWDEN, G.; PHILLIPS, T.M. & DELOVITCH, T.L. - Expression of Ia antigens by murine keratinizing epithelial Langerhans cells. Immunogenetics, 7: 465-478, 1978.
38. SHEPARD, C.C. - The experimental disease that follows the injection of human leprosy bacilli into footpads of mice. J. exp. Med., 112: 445-454, 1960.
39. SHEPRO, D.; COHEN, P.S. & KULA, N. - The incompetence of the hasmter cheek pouch membrane as a mechanical barrier to the movement of tritiated E.coli B3 and tritiated T4 bacteriophage. J. Immunol., 9: 725-731, 1964.
40. SILBERBERG-SINAKIN, I.; BAER, R.L. & THORBERCKE, G.J. - Langerhans cells. A review of their nature with emphasis on their immunologic functions. Progr. Allergy., 24: 268-271, 1976.
41. SINHORINI, I.L.; MERUSSE, J.L. & MARIANO, M. - Role of lymphatic drainage on the development of Calmette-Guérin Bacillus-induced granulomas in the hamster. Int. Arch. Allergy Immunol, 103: 166-174, 1994.
42. STINGL, G.; KATZ, S.I.; SHEVACH, E.M.; ROSENTHAL, A.S. & GREEN, I. - Analogous functions of macrophages and Langerhans cells in the initiation of immune response. J. invest. Derm., 71: 59-64, 1978.
43. STINGL, G.; KATZ, S.I.; SHEVACH, E.M.; WOLFF-SCHREINER, E. & GREEN, I. - Detection of Ia antigens on Langerhans cells in guinea pig skin. J. Immunol., 120: 570-578, 1978.
44. SUYA, H.; FUJIOKA, A.; PINCELLI, C.; FUKUYAMA, K. & EPSTEIN, W. - Skin granuloma formation in mice immunosupressed by cyclosporine. J. invest. Derm., 90: 430-433, 1988.
45. TANAKA, A.; EMORI, K.; NAGAO, S. et al. - Epithelioid granuloma formation requiring no T-cell function. Amer J. Path., 106: 165-170, 1982.
46. WEGELIUS, O. & HJELMMAN, G. - Vital staining of mast cells and fibrocytes. Acta path. microbiol. scand., 36: 304-308, 1955.

Correspondence to:

Maria Sueli Parreira de Arruda

Faculdade de Ciências, Departamento de Ciências Biológicas, UNESP

Av. Edmundo Coube, S/N

17033-360 Bauru, SP, BRASIL

FAX: 0142-304470, TELEX: 0142-312 Febu, TEL: 0142-302111

Publication Dates

Publication in this collection
21 Sept 2006
Date of issue
Aug 1995

History

Accepted
04 July 1995
Received
13 Jan 1955

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ADAMS, D.O. - The granulomatous inflammatory re sponse. A review. Amer. J. Path., 84: 164-191, 1976.

[2] 2. ARRUDA, M.S.P.; COELHO, K.I. & MONTENEGRO, M.R. - Experimental paracoceidioidomycosis in Syrian hamster inoculated in lhe cheek pouch. Mycopathologia (Den Haag), 128: 67-73, 1994.

[3] 3. ARRUDA, M.S.P.; FLEURY, R.N. & NOGUEIRA, M.E.S. - Inoculation of the Mycobacterium leprae into the hamster cheek pouch. Leprosy Rev., 65: 399-400, 1994.

[4] 4. ARRUDA, M.S.P. & MONTENEGRO, M.R. - Granulomatous reaction in the hamsters check pouch induced by killed Paracoccidioides brasiliensis. Braz. J. med. biol. Res., 28: 209-212, 1995.

[5] 5. BARKER, F. & BILLINGHAM, R.E. - Immunologically privileged sites. Advanc. Immunol., 25: 1-54, 1977.

[6] 6. BARKER, F. & BILLINGHAM, R.E. - The lymphatic status of hamster cheek pouch tissue in relation to its properties as a graft and as a graft site. J. exp. Med., 133: 620-639, 1971.

[7] 7. BERGSTRESSER, P.R.; FLETCHER, C.R. & STREILEIN, J.W. - Surface densities of Langerhans cells in relation to rodent epidermal sites with special immunologic properties. J. invest. Derm., 74: 77-80, 1980.

[8] 8. BIJOVSKY, A.T.; MILDER, R.V.; ABRAHAMSOHN, I.A.; SINHORINI, I.L. & MARIANO, M. - The influence of lymphatic drainage in experimental Trypanosoma cruzi infection. Acta trop. (Basel), 41: 207-214, 1984.

[9] 9. BJORK, J.; SMEDEGARD, G.; SVENSJO, E. & ARFORS, K.E. - The use of the hamster cheek pouch for intracavital microscopy studies of microvascular events. Progr. Appl. Microcirc., 6: 41-53, 1984.

[10] 10. BJORK, J. & SMEDEGARD, G. - The microvasculature of the hamster cheek pouch as a model for study acute immune-complex-induced inflammatory reactions. Int. Arch. Allergy, 74: 178-185, 1990.

[11] 11. BORIC, M.P. & ALBERTINI, R. - Atrial natriuretic peptide increases microvascular blood flow and macromolecular escape during renin infusion in hamster. Microcirc. Endoth. Lymph., 6: 67-88, 1990.

[12] 12. COELHO, K.I.R.; DeFAVERI, J.; RESKALLAH-IWASSO, M.T.; PERAÇOLI, M.T. & MOTA, N.G.S. - Paracoccidioidomicose experimental. In: DEL NEGRO, G.; LACAZ, C.S. & FIORILLO, A.M. Paracoccidioidomicose, blastomicose sul-americana. Săo Paulo, Sarvier, 1982.p. 69-84.

[13] 13. COVANT, H. & HARDY, M.H. - Stability of glandular metaplasia in hamster cheek pouch explants exposed to excess retinoids. Canad. Fed. Biol. Soc Proc., 26: 119, 1983.

[14] 14. DAVIS, M.J.; FERRER, P.N. & GORE, R.W. - Vascular anatomy and hydrostatic pressure profile in the hamster cheek pouch. Amer. J. Physiol., 250: H 291-303, 1986.

[15] 15. EPSTEIN, W.L.; FURUYAMA, K.; DANNOK, K. & KWAN-WONG, E. - Granulomatous inflammation in normal and athymic mice infected with Scliislosoma mansoni: an ultrastructural study. J. Path., 127: 207-215, 1979.

[16] 16. FRANCO.M.F.; MENDES, R.P.; MOSCARDI-BACCHI, M.; REZKALLAH-IWASSO, M.T. & MONTENEGRO, M.R.G. - Paracoccidioidomycosis. Baillicre's Clin. trop. Med. comm. Dis., 4: 185-220, 1989.

[17] 17. FULTON, G.P. & MAYNARD, F.L. - Effect of cortisone on tissue mast cells in the hamster cheek pouch. Proc. Soc. exp. Biol. (N.Y.), 84: 259-260, 1953.

[18] 18. GOLDENBERG, D.M. - Reduced lymphatic drainage from hamster cheek pouch: a proposed explanation of its immunologically privileged character. Experientia (Basel), 26: 907-908, 1970.

[19] 19. HARDY, M.H.; VRABLIC, O.E.; COVANT, H.A. & KANDARKAR, S.V. - The development of the Syrian hamster cheek pouch. Anat. Rec., 214: 273-282, 1986.

[20] 20. HASTING, R.C. - Leprosy. London, Churchill Livingstone, 1985.

[21] 21. HOFFSTEN, P.E. & DIXON, F.J. - Effect of irradiation and cyclophosphamide and anti-kill antibody formation in mice. J. Immunol., 112: 564-572, 1974.

[22] 22. KANDARKAR, S.V. & SIRSAT, S.M. - Developmental morphology of hamster cheek pouch epithelium. Folia morph. (Warszawa), 32: 345-351, 1984.

[23] 23. KAPLAN, H.J. & STREILEIN, J.W. - Do immunologically sites require a functioning spleen? Nature (Lond.), 251: 553-554, 1974.

[24] 24. KONG, Y.M.; SAVAGE, D. & KONG, L.N.L. - Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immils. J. Bact., 91: 876-883, 1966.

[25] 25. KRIPKE, M.L.; MUNN, C.G.; JEEVAN, A.; TANG, J. & BUCANA, C. - Evidence that cutaneous antigen - presenting cells migrate to regional lymph node during contact sensitization. J. Immunol., 45: 2833-2838, 1990.

[26] 26. LINDERMAN, R. & STRAULI, P. - Lymphatic vessels in the cheek pouch of the golden hamster. Transplantation, 6: 557-561, 1968.

[27] 27. MAIER, M. - The relation between allergy and immunity in leprosy. Int. J. Lcprosy, 55: 116-136, 1987.

[28] 28. MENDES-GIANNINI, M.J.; CAMARGO, M.E.; LACAZ, C.S. & FERREIRA, A.W. - Immunoenzymatic absorption test for serodiagnosis of paracoccidioidomycosis. J. clin. Microbiol., 20: 103-108, 1984.

[29] 29. MICHAL, L.M.; GIESSINGER, N. & SCHRDER, R. - Reduced thrombus formation in vivo after administration of pentoxifylline (Trentol). Thromb. Res., 56: 359-368, 1989.

[30] 30. MOCK, D. & MAIN, J.H.P. - Long-term organ culture of hamster cheek pouch. J. oral Path., 5: 237-240, 1976.

[31] 31. MOCK, D. & MAIN, J.H.P. - The effect of vitamin A on hamster cheek pouch mucosa in organ culture. J. dent. Res., 58: 635-637, 1979.

[32] 32. MYIAJI, M. & NISHIMURA, K. - Granuloma formation and killing functions of granuloma in congenitally athymic nude mice infected with Blastomyces dermatitides and Paracoccidioides brasiliensis. Mycopathologia (Den Haag), 82: 129-141, 1983.

[33] 33. OPROMOLLA, D.V.A. - Noçőes de hanseniase. Bauru, Centro de Estudos Dr. Reynaldo Quagliato, 1981.

[34] 34. RAUD, J.; DAHLEN, S.E.; SMEDEGARD, G. & HEDQVIST, P. - An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch. Acta physiol. scand., 135: 95-105, 1989.

[35] 35. RAUD, J. - Vasodilatalion and inhibition of mediator release represent two distinct mechanisms for prostaglandin modulation of acute mast cell-dependent inflammation. Brit. J. Pharmacol., 99: 449-454, 1990.

[36] 36. ROBINSON, M.E.; GIBBINS, A.M. & HARDY, M.H. - Persistence of retinoids in organ culture media during induction of mucous metaplasia and glandular morphogenesis in hamster cheek pouches. Experientia (Basel), 15: 513-517, 1990.

[37] 37. ROWDEN, G.; PHILLIPS, T.M. & DELOVITCH, T.L. - Expression of Ia antigens by murine keratinizing epithelial Langerhans cells. Immunogenetics, 7: 465-478, 1978.

[38] 38. SHEPARD, C.C. - The experimental disease that follows the injection of human leprosy bacilli into footpads of mice. J. exp. Med., 112: 445-454, 1960.

[39] 39. SHEPRO, D.; COHEN, P.S. & KULA, N. - The incompetence of the hasmter cheek pouch membrane as a mechanical barrier to the movement of tritiated E.coli B3 and tritiated T4 bacteriophage. J. Immunol., 9: 725-731, 1964.

[40] 40. SILBERBERG-SINAKIN, I.; BAER, R.L. & THORBERCKE, G.J. - Langerhans cells. A review of their nature with emphasis on their immunologic functions. Progr. Allergy., 24: 268-271, 1976.

[41] 41. SINHORINI, I.L.; MERUSSE, J.L. & MARIANO, M. - Role of lymphatic drainage on the development of Calmette-Guérin Bacillus-induced granulomas in the hamster. Int. Arch. Allergy Immunol, 103: 166-174, 1994.

[42] 42. STINGL, G.; KATZ, S.I.; SHEVACH, E.M.; ROSENTHAL, A.S. & GREEN, I. - Analogous functions of macrophages and Langerhans cells in the initiation of immune response. J. invest. Derm., 71: 59-64, 1978.

[43] 43. STINGL, G.; KATZ, S.I.; SHEVACH, E.M.; WOLFF-SCHREINER, E. & GREEN, I. - Detection of Ia antigens on Langerhans cells in guinea pig skin. J. Immunol., 120: 570-578, 1978.

[44] 44. SUYA, H.; FUJIOKA, A.; PINCELLI, C.; FUKUYAMA, K. & EPSTEIN, W. - Skin granuloma formation in mice immunosupressed by cyclosporine. J. invest. Derm., 90: 430-433, 1988.

[45] 45. TANAKA, A.; EMORI, K.; NAGAO, S. et al. - Epithelioid granuloma formation requiring no T-cell function. Amer J. Path., 106: 165-170, 1982.

[46] 46. WEGELIUS, O. & HJELMMAN, G. - Vital staining of mast cells and fibrocytes. Acta path. microbiol. scand., 36: 304-308, 1955.