title: CK2 Secreted by Leishmania braziliensis Mediates Macrophage Association Invasion: A Comparative Study between Virulent and Avirulent Promastigotes.
abstract: CK2 is a protein kinase distributed in different compartments of Leishmania braziliensis: an externally oriented ecto-CK2, an intracellular CK2, and a secreted CK2. This latter form is constitutively secreted from the parasite (CsCK2), but such secretion may be highly enhanced by the association of specific molecules, including enzyme substrates, which lead to a higher enzymatic activity, called inductively secreted CK2 (IsCK2). Here, we examined the influence of secreted CK2 (sCK2) activity on the infectivity of a virulent L. braziliensis strain. The virulent strain presented 121-fold higher total CK2 activity than those found in an avirulent strain. The use of specific CK2 inhibitors (TBB, DRB, or heparin) inhibited virulent parasite growth, whereas no effect was observed in the avirulent parasites. When these inhibitors were added to the interaction assays between the virulent L. braziliensis strain and macrophages, association index was drastically inhibited. Polyamines enhanced sCK2 activity and increased the association index between parasites and macrophages. Finally, sCK2 and the supernatant of the virulent strain increased the association index between the avirulent strain and macrophages, which was inhibited by TBB. Thus, the kinase enzyme CK2 seems to be important to invasion mechanisms of L. braziliensis.
authors.affiliation: Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Rua Professor Manuel de Abreu, 444, Pavilhão Américo Piquet Carneiro, 5° Andar, 20550-170 Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Madeira Brito
authors.initials: AM
authors.lastname: Zylbersztejn
authors.affiliation: Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Rua Professor Manuel de Abreu, 444, Pavilhão Américo Piquet Carneiro, 5° Andar, 20550-170 Rio de Janeiro, RJ, Brazil ; Programa de Pós Graduação em Microbiologia/FCM/UERJ, Av. Professor Manuel de Abreu, 444, Pavilhão Américo Piquet Carneiro, 3° andar, Vila Isabel, 20550-170, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos Gustavo Vieira
authors.initials: CG
authors.lastname: de Morais
authors.affiliation: Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Rua Professor Manuel de Abreu, 444, Pavilhão Américo Piquet Carneiro, 5° Andar, 20550-170 Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Karina Castro
authors.initials: AK
authors.lastname: Lima
authors.affiliation: Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Rua Professor Manuel de Abreu, 444, Pavilhão Américo Piquet Carneiro, 5° Andar, 20550-170 Rio de Janeiro, RJ, Brazil.
authors.forename: Joyce Eliza de Oliveira
authors.initials: JE
authors.lastname: Souza
authors.affiliation: Instituto de Microbiologia Paulo de Góes-CCS, Universidade Federal do Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho, 373, CCS, Bloco I, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Angela Hampshire
authors.initials: AH
authors.lastname: Lopes
authors.affiliation: Laboratório de Imunofarmacologia Parasitária, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Rua Professor Manuel de Abreu 444, Pavilhão Américo Piquet Carneiro, 5° Andar, 20550-170 Rio de Janeiro, RJ, Brazil.
authors.forename: Sílvia Amaral Gonçalves
authors.initials: SA
authors.lastname: Da-Silva
authors.affiliation: Laboratório de Sinalização Celular, Instituto de Bioquímica Médica-CCS, Universidade Federal do Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho, 373, CCS, Bloco H, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Mário Alberto Cardoso
authors.initials: MA
authors.lastname: Silva-Neto
authors.affiliation: Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Rua Professor Manuel de Abreu, 444, Pavilhão Américo Piquet Carneiro, 5° Andar, 20550-170 Rio de Janeiro, RJ, Brazil.
authors.forename: Patrícia Maria Lourenço
authors.initials: PM
authors.lastname: Dutra
mesh_terms: D000818:Animals; D047390:Casein Kinase II / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007892:Leishmania braziliensis / Q000201:enzymology* / Q000276:immunology / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D047390:Casein Kinase II