title: Early events in initiation of alternative complement pathway activation by the capsule of Cryptococcus neoformans.
abstract: The capsule of Cryptococcus neoformans is a powerful activator of the alternative complement pathway. This study examined the manner in which the cryptococcal capsule influences initiation of and early events in complement activation by C. neoformans. These studies examined the effects of the classical and alternative pathways on the kinetics and early sites for deposition of C3 fragments on encapsulated cryptococci, nonencapsulated cryptococci, and zymosan. The results showed that nonencapsulated cryptococci and zymosan are qualitatively and quantitatively similar in the manner in which they initiate complement activation. Both utilize the classical and alternative pathways. Initiation via the classical pathway occurs suddenly and simultaneously at sites distributed over the entire cell surface. Initiation of the alternative pathway by zymosan and nonencapsulated cryptococci is characterized by a lag of 6 to 8 min before appreciable amounts of C3 accumulate on the cells. Alternative pathway initiation by zymosan and nonencapsulated cryptococci occurs at a limited number of focal initiation sites that expand with alternative pathway amplification to cover the cell surface. Presence of the cryptococcal capsule blocks classical pathway initiation, which would normally occur at the cryptococcal cell wall, and produces an initiation that is dependent solely on the alternative pathway. Initiation of the alternative pathway by the cryptococcal capsule is characterized by a lag in C3 accumulation and the appearance of a limited number of focal initiation sites which resemble those observed when the alternative pathway is activated by zymosan and nonencapsulated cryptococci.
authors.affiliation: Department of Microbiology, University of Nevada, Reno 89557.
authors.forename: T R
authors.initials: TR
authors.lastname: Kozel
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: J W
authors.initials: JW
authors.lastname: Murphy
mesh_terms: D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D003180:Complement C3b Inactivator Proteins / Q000276:immunology; D017242:Complement Factor H; D003170:Complement Pathway, Alternative / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000276:immunology*; D015054:Zymosan / Q000276:immunology
chemical_list: C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D017242:Complement Factor H; D015054:Zymosan