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Clinical and Diagnostic Laboratory Immunology, January 2002, p. 144-148, Vol. 9, No. 1
1071-412X/01/$04.00+0     DOI: 10.1128/CDLI.9.1.144-148.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Activation of the Alternative Complement Pathway by Fungal Melanins

Department of Microbiology and Immunology,¹ Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York,³ Department of Microbiology, School of Medicine, University of Nevada, Reno, Nevada²

Received 23 March 2001/ Returned for modification 23 July 2001/ Accepted 19 October 2001

Melanins are complex biological pigments formed by the oxidative polymerization of phenolic and/or indolic compounds. These pigments have been implicated in the pathogenesis of some microbial infections, malignancies, degenerative disorders, and autoimmune diseases. Recent studies have demonstrated that melanins have antigenic and anti-inflammatory properties. These findings led us to further explore the interaction of melanins with the immune system. Melanin particles ("ghosts") were isolated from in vitro-melanized Cryptococcus neoformans cells and Aspergillus niger conidia and then incubated in normal human serum containing ¹²⁵I-labeled complement C3. The results demonstrated deposition of C3 fragments onto the melanin ghosts as early as 1 min after incubation, with maximum deposition occurring after 12 min for C. neoformans-derived melanin ghosts and after 25 min for A. niger-derived melanin ghosts. The blocking of classical pathway activation did not affect the kinetics or total deposition of C3 onto the melanin ghosts, indicating that melanins activate complement through the alternative pathway. Immunofluorescence analysis of lungs from BALB/c mice injected intratracheally with C. neoformans-derived melanin ghosts demonstrated deposition of C3 fragments onto the ghosts. Small granulomas were also observed surrounding the ghosts. However, melanization of the C. neoformans cell wall did not alter the kinetics or total deposition of C3 fragments onto the fungal cells. The finding that melanin surfaces can activate the complement system suggests a potential mechanism for the pathogenesis of some degenerative and/or autoimmune processes that involve melanized cells as well as another potential role for melanin in the virulence of melanin-producing microorganisms.

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