Patogenia da leishmaniose cutânea experimental: a importância da necrose na eliminação dos parasitos das lesões

Andrade, Zilton A.; Reed, Steven G.; Roters, Silene B.; Sadigursky, Moysés

doi:10.1590/S0037-86821984000400005

Resumos

Um estudo histopatológico e ultraestrutural das lesões da leishmaniose cutânea causada pela Leishmania mexicana amazonensis em duas cepas isogênicas de camundongo, uma susceptível (Balb/c) e outra resistente (A/J), demonstrou que os amastigotas ficavam bem preservados nos vacúolos parasitóforos dos macrófagos, igualmente em ambas as cepas. A reação de imunofluorescência revelou antigenos parasitários no interior e na membrana dos macrófagos de maneira idêntica para ambas as cepas. A diferença ocorria quando os macrófagos apareciam destruídos e as leishmanias ficavam livres ou fagocitadas por polimorfonucleares, neutrófilos e eosinófilos. Estes parasitos exibiam então graus variáveis de nítidas alterações degenerativas. No camundongo resistence, a necrose, de tipo caseoso ou fibrinóide, era mais disseminada e mais freqüente que no animal susceptível. Os achados observados indicaram que as leishmanias não são destruídas no interior dos macrófagos e sim fora deles, especialmente quando fagocitadas por leucócitos polimorfonucleares. A necrose apareceu como o mecanismo mais saliente através do qual o hospedeiro elimina os parasitos das lesões, sendo a mesma um aspecto importante da reação de hipersensibilidade tardia que ocorre nos animais resistentes.

Leishmaniose cutânea experimental; Camundongos Balb/c e A/J; Leishmania mexicana amazonensis; Necrose tíssular fibrinóide; Necrose tissular caseosa; Necrose tissular purulenta

Amastigotes of Leshmania mexicana amazonensis appeared healthy and well preserved within the parasitophorous vacuoles of macrophages during the infection of a susceptible (Balb/c) or a relatively resistant (A/J) inbred strain of mice. Immunofluorescence showed the presence of leishmanial antigens within infected macrophages and in their external membranes similar for both strains. When the amastigotes were found extracellularly or within polymorphonuclear neutrophils or eosinophils, marked ultrastructural degenerative changes were observed in them. Such necrotic alterations were seen frequently in the resistant mice and rarely in the susceptible ones. Thus, necrosis of parasitized macrophages appeared as a major mechanism through which the resistant host eliminates the parasites from the lesions. It may be considered as a histological marker of resistance in leishmaniasis and represents a prominent component of the delayed-type immunological mechanism occurring in resistant hosts.

Experimental cutaneous leishmaniasis; Balb/c and A/J mice; Leishmania mexicana amazonensis; Fibrinoid tissue necrosis; Caseous tissue necrosis; Purulent tissue necrosis

ARTIGOS

Patogenia da leishmaniose cutânea experimental. A importância da necrose na eliminação dos parasitos das lesões

Zilton A. Andrade; Steven G. Reed; Silene B. Roters; Moysés Sadigursky

RESUMO

Um estudo histopatológico e ultraestrutural das lesões da leishmaniose cutânea causada pela Leishmania mexicana amazonensis em duas cepas isogênicas de camundongo, uma susceptível (Balb/c) e outra resistente (A/J), demonstrou que os amastigotas ficavam bem preservados nos vacúolos parasitóforos dos macrófagos, igualmente em ambas as cepas. A reação de imunofluorescência revelou antigenos parasitários no interior e na membrana dos macrófagos de maneira idêntica para ambas as cepas. A diferença ocorria quando os macrófagos apareciam destruídos e as leishmanias ficavam livres ou fagocitadas por polimorfonucleares, neutrófilos e eosinófilos. Estes parasitos exibiam então graus variáveis de nítidas alterações degenerativas. No camundongo resistence, a necrose, de tipo caseoso ou fibrinóide, era mais disseminada e mais freqüente que no animal susceptível. Os achados observados indicaram que as leishmanias não são destruídas no interior dos macrófagos e sim fora deles, especialmente quando fagocitadas por leucócitos polimorfonucleares. A necrose apareceu como o mecanismo mais saliente através do qual o hospedeiro elimina os parasitos das lesões, sendo a mesma um aspecto importante da reação de hipersensibilidade tardia que ocorre nos animais resistentes.

Palavras-chave: Leishmaniose cutânea experimental. Camundongos Balb/c e A/J. Leishmania mexicana amazonensis. Necrose tíssular fibrinóide. Necrose tissular caseosa. Necrose tissular purulenta.

ABSTRACT

Amastigotes of Leshmania mexicana amazonensis appeared healthy and well preserved within the parasitophorous vacuoles of macrophages during the infection of a susceptible (Balb/c) or a relatively resistant (A/J) inbred strain of mice. Immunofluorescence showed the presence of leishmanial antigens within infected macrophages and in their external membranes similar for both strains. When the amastigotes were found extracellularly or within polymorphonuclear neutrophils or eosinophils, marked ultrastructural degenerative changes were observed in them. Such necrotic alterations were seen frequently in the resistant mice and rarely in the susceptible ones. Thus, necrosis of parasitized macrophages appeared as a major mechanism through which the resistant host eliminates the parasites from the lesions. It may be considered as a histological marker of resistance in leishmaniasis and represents a prominent component of the delayed-type immunological mechanism occurring in resistant hosts.

Keywords: Experimental cutaneous leishmaniasis. Balb/c and A/J mice. Leishmania mexicana amazonensis. Fibrinoid tissue necrosis. Caseous tissue necrosis. Purulent tissue necrosis.

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Recebido para publicação em 30/7/1984.

Centro de Pesquisas Gonçalo Moniz (FIOCRUZ/UFBA) Salvador, Bahia, com apoio dos Institutos Nacionais de Saúde, USA (Grant n.° 16282) e da FINEP (Convênio 43.82.0094.00).

1. Alexandre J, VickermanK. Fusionofhostcell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana infected macrophages. Journal of Protozoology 22: 502-508, 1975.
2. Andrade ZA, Reed SG, Roters SB, Sadigursky M. Immunopathology of experimental cutaneous leishmaniasis. American Journal of Pathology 114:137-148, 1984.
3. Berman JDS, Dwyer DM. Expression of leishmania antigen on the surface membrane of infected human macrophages in vitro. Clinical and Experimental Immunology 44:342-348, 1981.
4. Berman JDS, Dwyer DM, Wyler DJ. Multiplication of Leishmania in human macrophages in vitro. Infection and Immunity 26:375-379, 1979.
5. Bryceson ADM, Bray RS, Wolstencroft RA, Dumonde DC. Immunity in cutaneous leishmaniasis of guinea-pig. Clinical and Experimental Immunology 7:301-341, 1970.
6. Buchmüller YS, Manuel J. Studies onthe mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from Concanavalin A-stimulated lymphocytes. Journal of Experimental Medicine 150:359-370, 1979.
7. Chang PK. Leishmanicidal mechanisms of human polymorphonuclear phagocytes. American Journal of Tropical Medicine and Hygiene 30:322-333, 1981.
8. Chang PK, Chiao JW. Cellular immunity of mice to Leishmania donovani in vitro: lymphokine-mediated killing of intracellular parasites in macrophages. Proceedings of the National Academy of Sciences 78:7083- 7087, 1981.
9. Chang PK, Dwyer DM. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science 193:678-680, 1976.
10. Deane L, Guimarães FN. Aspectos interessantes de phagocytose observados na leishmaniose visceral e na malária. Memórias do Instituto Oswaldo Cruz 33:263- 279, 1938.
11. Farah FS, Samra SA, Nuwayri-Salti N. The role of macrophage in cutaneous leishmaniasis. Immunology 29:755-764, 1975.
12. Haidaris CG, Bonventre PF. Elimination of Leishmania donovani amastigotes by activated macrophages. Infection and Immunity 33:918-926, 1981.
13. Howard JG, Hale C, Liew FY. Genetically determined response mechanisms to cutaneous leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 76:152-154, 1982.
14. Lewis DH, Peters W. The resistance of intracellular Leishmania parasites to digestion by lysosomal enzymes. Annals of Tropical Medicine and Parasitology 71:295- 312, 1977.
15. Mauel J, Behin R. Immunology of leishmaniasis. In: Levanwsky M, Hutner SH, (ed) Biochemistry and physiology of Protozoa 2^nd edition, vol. 4 p. 385-429, Academic Press, New York, 1981.
16. Monroy A, Ridley DS, Heather CJ, Ridley MJ. Histological studies on the elimination oi Leishmania enrietti from skin lesions in the guinea-pig. British Journal of Experimental Pathology 61:601-610, 1980.
17. Nacy CA, Meltzer MS, Leonard EJ, Wyler D. Intracellular replication and lymphokine-induced destruction of Leishmania tropica in C₃H/HeN mouse macrophages. Journal of Immunology 127:2381-2386, 1981.
18. Pérez H. Factors influencing the host response to Leishmania mexicana Cytopathology of parasitic diseases. Ciba Foundation Symposium 99: 157-173. Pitman Books, London, 1983.
19. Ridley DS. The pathogenesis of cutaneous leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 73: 150-160, 1979.
20. Scott P, Sacks D, Sher A. Resistance to macrophage- mediated killing as a factor influencing the pathogenesis of chronic cutaneous leishmaniasis. Journal of Immunology 131:966-971, 1983.
21. Sher A, Sacks DL, Scott PA. Host and parasite factors influencing the expression of cutaneous leishmaniasis. Cytopathology of parasitic disease. Ciba Foundation Symposium 99: 174-189. Pitman Books, London, 1983.

Datas de Publicação

Publicação nesta coleção
07 Jun 2013
Data do Fascículo
Dez 1984

Histórico

Recebido
30 Jul 1984
Aceito
30 Jul 1984

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

[1] 1. Alexandre J, VickermanK. Fusionofhostcell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana infected macrophages. Journal of Protozoology 22: 502-508, 1975.

[2] 2. Andrade ZA, Reed SG, Roters SB, Sadigursky M. Immunopathology of experimental cutaneous leishmaniasis. American Journal of Pathology 114:137-148, 1984.

[3] 3. Berman JDS, Dwyer DM. Expression of leishmania antigen on the surface membrane of infected human macrophages in vitro. Clinical and Experimental Immunology 44:342-348, 1981.

[4] 4. Berman JDS, Dwyer DM, Wyler DJ. Multiplication of Leishmania in human macrophages in vitro. Infection and Immunity 26:375-379, 1979.

[5] 5. Bryceson ADM, Bray RS, Wolstencroft RA, Dumonde DC. Immunity in cutaneous leishmaniasis of guinea-pig. Clinical and Experimental Immunology 7:301-341, 1970.

[6] 6. Buchmüller YS, Manuel J. Studies onthe mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from Concanavalin A-stimulated lymphocytes. Journal of Experimental Medicine 150:359-370, 1979.

[7] 7. Chang PK. Leishmanicidal mechanisms of human polymorphonuclear phagocytes. American Journal of Tropical Medicine and Hygiene 30:322-333, 1981.

[8] 8. Chang PK, Chiao JW. Cellular immunity of mice to Leishmania donovani in vitro: lymphokine-mediated killing of intracellular parasites in macrophages. Proceedings of the National Academy of Sciences 78:7083- 7087, 1981.

[9] 9. Chang PK, Dwyer DM. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science 193:678-680, 1976.

[10] 10. Deane L, Guimarães FN. Aspectos interessantes de phagocytose observados na leishmaniose visceral e na malária. Memórias do Instituto Oswaldo Cruz 33:263- 279, 1938.

[11] 11. Farah FS, Samra SA, Nuwayri-Salti N. The role of macrophage in cutaneous leishmaniasis. Immunology 29:755-764, 1975.

[12] 12. Haidaris CG, Bonventre PF. Elimination of Leishmania donovani amastigotes by activated macrophages. Infection and Immunity 33:918-926, 1981.

[13] 13. Howard JG, Hale C, Liew FY. Genetically determined response mechanisms to cutaneous leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 76:152-154, 1982.

[14] 14. Lewis DH, Peters W. The resistance of intracellular Leishmania parasites to digestion by lysosomal enzymes. Annals of Tropical Medicine and Parasitology 71:295- 312, 1977.

[15] 15. Mauel J, Behin R. Immunology of leishmaniasis. In: Levanwsky M, Hutner SH, (ed) Biochemistry and physiology of Protozoa 2^nd edition, vol. 4 p. 385-429, Academic Press, New York, 1981.

[16] 16. Monroy A, Ridley DS, Heather CJ, Ridley MJ. Histological studies on the elimination oi Leishmania enrietti from skin lesions in the guinea-pig. British Journal of Experimental Pathology 61:601-610, 1980.

[17] 17. Nacy CA, Meltzer MS, Leonard EJ, Wyler D. Intracellular replication and lymphokine-induced destruction of Leishmania tropica in C₃H/HeN mouse macrophages. Journal of Immunology 127:2381-2386, 1981.

[18] 18. Pérez H. Factors influencing the host response to Leishmania mexicana Cytopathology of parasitic diseases. Ciba Foundation Symposium 99: 157-173. Pitman Books, London, 1983.

[19] 19. Ridley DS. The pathogenesis of cutaneous leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 73: 150-160, 1979.

[20] 20. Scott P, Sacks D, Sher A. Resistance to macrophage- mediated killing as a factor influencing the pathogenesis of chronic cutaneous leishmaniasis. Journal of Immunology 131:966-971, 1983.

[21] 21. Sher A, Sacks DL, Scott PA. Host and parasite factors influencing the expression of cutaneous leishmaniasis. Cytopathology of parasitic disease. Ciba Foundation Symposium 99: 174-189. Pitman Books, London, 1983.

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Patogenia da leishmaniose cutânea experimental: a importância da necrose na eliminação dos parasitos das lesões

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