Skip to main content

Advertisement

SpringerLink
Log in

Soluble Components of Histoplasma Capsulatum var. Capsulatum have Hemagglutinin Activity and Induce Syngeneic Hemophagocytosis In Vitro

  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Histoplasma capsulatum var. capsulatum is a thermally dimorphic fungus that causes histoplasmosis. Fungal hemagglutination activity and cases of reactive hemophagocytic syndrome (RHS) have been reported in the disseminated form of disease. In the present study, soluble components of H. capsulatum var. capsulatum have been investigated for hemagglutinin activity and the capacity to induce hemophagocytosis in the mouse system. To analyze hemagglutinating activity, mouse red blood cells (RBC) (1% v/v in PBS) were incubated (37°C, 1 h) with cell-free antigen (CFAg) from H. capsulatum var. capsulatum (isolate IMT/HC128) (RBC-CFAg) or previously heated CFAg (56°C, 30 min) (RBC-hCFAg) or as control with PBS (RBC-PBS). Hemophagocytosis was analyzed by incubating BALB/c mouse peritoneal phagocytic cells (5 × 106 cells) with syngeneic RBC, sensitized or not with CFAg. In addition, mouse polyclonal antibodies were raised against syngeneic RBC-CFAg (anti-RBC-CFAg) and used to analyze CFAg chromatographic fractions (Sephadex G75/120) by immunoenzymatic assay (ELISA). Hemagglutinin activity was observed with RBC-CFAg, but not with RBC-hCFAg or RBC. Also, hemophagocytosis was observed with RBC-CFAg, but not with RBC. The anti-RBC-CFAg antibodies reacted with CFAg fractions corresponding to a molecular mass (MM) higher than 150 kDa. In conclusion, the yeast form of H. capsulatum var. capsulatum releases thermolabile soluble components with hemagglutinin activity and it has been demonstrated for the first time that soluble components of the same fungus induce syngeneic hemophagocytosis in the in vitro mouse system. Also, indirect analysis with antibodies suggests that high-MM components (>150 kDa) are responsible for the interaction with RBC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Reyes-Montes MDR, Taylor ML, Curiel-Quesada E, et al. Current knowledge on the strain typing of the pathogenic fungus Histoplasma capsulatum var. capsulatum: a review of the findings. Rev Iberoam Micol. 2000;17:121–6.

    Google Scholar 

  2. Wheat LJ, Cloud G, Johnson PC, et al. Clearance of fungal burden during treatment of disseminated histoplasmoses with liposomal amphotericin B versus itraconazole. Antimicrob Agents Chemother. 2001;45:2354–7.

    Article  CAS  PubMed  Google Scholar 

  3. Leimann BCQ, Pizzini CV, Muniz MM, et al. Histoplasmosis in a Brazilian center clinical forms and laboratory tests. Rev Iberoamer Micol. 2005;22:141–6.

    Article  Google Scholar 

  4. Eissenberg LG, Goldman WE. Histoplasma variation and adaptive strategies for parasitism: new perspectives on histoplasmosis. Clin Microbiol Rev. 1991;4:411–21.

    CAS  PubMed  Google Scholar 

  5. Wheat LJ, Sarosi G, McKinsey D, Hamill R, et al. Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30:688–95.

    Article  CAS  PubMed  Google Scholar 

  6. Rachid A, Rezende LS, Moura SF, et al. A case study of disseminated histoplasmosis linked to common variable immunodeficiency. Braz J Infect Dis. 2003;7:268–72.

    Article  PubMed  Google Scholar 

  7. Tsuda H. Hemophagocytic syndrome (HPS) in children and adults. Int J Hematol. 1997;65:215–26.

    Article  CAS  PubMed  Google Scholar 

  8. Wang Z, Duarte AG, Scnadig J. Fatal reactive hemophagocytosis related to disseminated histoplasmosis with endocarditis: an unusual case diagnosed at autopsy. South Med Assoc. 2006;100:208–11.

    Google Scholar 

  9. Guiot HM, Bertrán-Pasarell J, Tormos LM, et al. Ileal perforation and reactive hemophagocytic syndrome in a patient with disseminated histoplasmosis: the role of real-time polymerase chain reaction in the diagnosis and successful treatment with amphotericin B lipid complex. Diagn Microbiol Infect Dis. 2007;57:429–33.

    Article  PubMed  Google Scholar 

  10. Janka G, Imashuku S, Elinder G, et al. Infection and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am. 1998;12:435–44.

    Article  CAS  PubMed  Google Scholar 

  11. Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6:601–8.

    Article  CAS  PubMed  Google Scholar 

  12. Janka G, Stadt UZ. Familial and acquired hemophagocytic lymphohistiocytosis. Hematol Am Soc Hematol Educ Program. 2005;5:82–8.

    Google Scholar 

  13. Taylor ML, Duarte-Escalante E, Pérez A, et al. Histoplasma capsulatum yeast cells attach and agglutinate human erythrocytes. Med Mycol. 2004;42:287–92.

    Article  CAS  PubMed  Google Scholar 

  14. Sá-Nunes A, Medeiros AI, Nicolete R, et al. Efficacy of cell-free antigens in evaluating cell immunity and inducing protection in a murine model of histoplasmosis. Microbes Infect. 2005;7:584–92.

    PubMed  Google Scholar 

  15. Camargo ZP, Taborda CP, Rodrigues EG, Travassos LR. The use of cell-free antigens of Paracoccidioides brasiliensis in serological tests. J Med Vet Mycol. 1991;29:31–8.

    Article  CAS  PubMed  Google Scholar 

  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–75.

    CAS  PubMed  Google Scholar 

  17. Fujiwara F, Hibbi S, Imashuku S. Hypercytokinemia and hemophagocytic syndrome. Am J Pediatr Hematol Oncol. 1993;15:92–8.

    Article  CAS  PubMed  Google Scholar 

  18. Ohga S, Maatsuzaki A, Nishizaki M. Inflammatory cytokines in virus-associated hemophagocytic syndrome: interferon gamma as a sensitive indicator of disease activity. Am J Pediatr Hematol Oncol. 1993;15:291–8.

    CAS  PubMed  Google Scholar 

  19. Durkin MM, Connolly PAA, Wheat LJ. Comparison of radioimmunoassay and enzyme-linked immunoassay methods for detection of Histoplasma capsulatum var. capsulatum antigen. J Clin Microbiol. 1997;35:2252–5.

    CAS  PubMed  Google Scholar 

  20. Wheat LJ, Garringer T, Brizendine E, Connolly P. Diagnosis of histoplasmosis by antigen detection based upon experience at the histoplasmosis reference laboratory. Diagn Microbiol Infect Dis. 2002;43:29–37.

    Article  CAS  PubMed  Google Scholar 

  21. Bullock WE, Artz RP, Bhathena D, Tung KS. Histoplasmosis. Arch Intern Med. 1979;139:700–2.

    Article  CAS  PubMed  Google Scholar 

  22. Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007;20:115–32.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Fundação Araucária/PR, Fundação de Apoio ao Ensino, Pesquisa e Extensão (FAEP/UEL), Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Japan International Cooperation Agency (JICA). The authors thank Timothy J. C. Roberts for the correction of the English text.

Author information

Authors and Affiliations

  1. Departamento de Ciências Patológicas, CCB, Universidade Estadual de Londrina, Campus Universitário, Londrina, PR, 86051-970, Brazil

    R. H. F. Vivan, P. C. Leonello, L. A. Nagashima, M. S. Kaminami, F. S. M. Tristão, M. A. Ono & E. N. Itano

  2. Medical Mycology Research Center, Chiba University, Chiba, Japan

    A. Sano

  3. Tropical Medicine Institute, IMT, Lima, Peru

    C. V. Béjar

Authors
  1. R. H. F. Vivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. C. Leonello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. A. Nagashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. S. Kaminami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. S. M. Tristão
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Sano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. A. Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. V. Béjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. N. Itano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. N. Itano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vivan, R.H.F., Leonello, P.C., Nagashima, L.A. et al. Soluble Components of Histoplasma Capsulatum var. Capsulatum have Hemagglutinin Activity and Induce Syngeneic Hemophagocytosis In Vitro. Mycopathologia 169, 151–157 (2010). https://doi.org/10.1007/s11046-009-9243-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-009-9243-3

Keywords

Search

Navigation