Burst oxidativo dos neutrófilos humanos: estudo da influência do polimorfismo do receptor para IgG FeyRIIIb na cooperação com os receptores para complemento
Carregando...
Data
2008-05-09
Autores
Urbaczek, Ana Carolina [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os receptores para a porção Fc das IgG (FcgR) estão amplamente expressos nas células do sistema imune e podem estimular uma variedade de respostas efetoras. Três classes de FcgR são descritas nos humanos: FcgRI, FcgRII e FcgRIII. O neutrófilo expressa constitutivamente as isoformas FcgRIIa (CD32) e FcgRIIIb (CD16), as quais apresentam um polimorfismo funcional decorrente do polimorfismo alélico. No FcgRIIa, a substituição da histidina (H) pela arginina (R) na posição 131 resulta nas variantes polimórficas FcgRIIa- R131 e FcgRIIa-H131, que diferem quanto à capacidade de ligação à IgG2 humana. Quanto ao FcgRIIIb (CD16), o polimorfismo genético é responsável pela expressão dos antígenos de neutrófilo (NA)1, NA2 e SH e resulta em um maior número de sítios de glicosilação em NA2. O FcgRIIIb é responsável pela aproximação dos ligantes na membrana para o FcgRIIa e também interage com o receptor para complemento tipo 3 (CR3) na superfície celular. A cooperação entre os FcgRIIa/IIIb com o CR3 promove a estimulação máxima das respostas do neutrófilo, dentre elas o burst oxidativo. Uma vez que a interação FcgRIIIb/CR3 ocorre via sítio de ligação lectina-sacarídeo, o objetivo deste estudo foi avaliar se o polimorfismo alélico do FcgRIIIb poderia afetar a cooperação entre os FcgR e os CR em mediar o burst oxidativo dos neutrófilos. As freqüências dos alelos H/R-131 e NA1/NA2/SH foram analisadas por genotipagem com oligonucleotídeos alelo-específicos e reação em cadeia da polimerase e a densidade de expressão dos receptores (FcgRIIa, FcgRIIIb, CR1 e CR3) foi determinada por citometria de fluxo. A distribuição dos genótipos para o FcgRIIIb (n=169) foi NA1/NA2 (52,1%), NA2 (27,8%) e NA1 (20,1%). Dentre 174 indivíduos, apenas 6,3% apresentaram o gene SH. Quanto aos genótipos para o FcgRIIa (n=143), a distribuição...
Receptors for immunoglobulin G (FcgR) are known to be expressed on many cells of the immune system and they can trigger a variety of biological responses. Human FcgR belong to the Ig superfamily and three classes of these receptors have been recognized: FcgRI, FcgRII and FcgRIIl, with different affinities and specificities for IgG subclasses. Neutrophils express the FcgRIIa (CD32) and FcgRIIlb (CD16) isoforms, which display a functional polymorphism due to biallelic polymorphisms. In the case of FcgRIIa, an arginine (FcgRIIa-R131) or histidine (FcgRIIa-H131) at amino acid position 131 determines receptor affinity for IgG2, FcgRIIa-H131 being the isoform with highest affinity. On neutrophils, the FcgRIIIb bears the neutrophil antigen (NA) polymorphism, NA1, NA2 and SH, NA2 being the more glycosylated isoform. Cooperation of FcgRIIIb with FcgRIIa and CR3 (complement receptor type 3) is necessary for efficient neutrophil responses, including the oxidative burst. Since the FcgRIIIb/CR3 cooperation occurs via lectin-sacharide-like interaction, the aim of this study was to evaluate whether the allelic polymorphism, NA1 and NA2, could influence the cooperation of FcgRIIIb with CR3 in mediating the oxidative burst of neutrophils. FcgRIIa and FcgRIIIb genotyping analysis were performed by polymerase chain reaction with allelespecific primers and surface expressions of FcgRIIa, FcgRIIIb, CR1 and CR3 on neutrophils were determined by flow cytometry. The FcgRIIIb genotype distribution (n=169) was NA1/NA2 (52.1%), NA2 (27.8%) and NA1 (20.1%). SH gene was found in 11 (6.3%) volunteers from 174 subjects. With respect to the FcgRIIa genotype (n=143), the distribution observed was R131 (41.2%), H/R131 (38.5%) and H (20.3%). Neutrophils were stimulated with immune complexes (IC)-IgG opsonized or not with complement and the oxidative burst... (Complete abstract click electronic access below)
Receptors for immunoglobulin G (FcgR) are known to be expressed on many cells of the immune system and they can trigger a variety of biological responses. Human FcgR belong to the Ig superfamily and three classes of these receptors have been recognized: FcgRI, FcgRII and FcgRIIl, with different affinities and specificities for IgG subclasses. Neutrophils express the FcgRIIa (CD32) and FcgRIIlb (CD16) isoforms, which display a functional polymorphism due to biallelic polymorphisms. In the case of FcgRIIa, an arginine (FcgRIIa-R131) or histidine (FcgRIIa-H131) at amino acid position 131 determines receptor affinity for IgG2, FcgRIIa-H131 being the isoform with highest affinity. On neutrophils, the FcgRIIIb bears the neutrophil antigen (NA) polymorphism, NA1, NA2 and SH, NA2 being the more glycosylated isoform. Cooperation of FcgRIIIb with FcgRIIa and CR3 (complement receptor type 3) is necessary for efficient neutrophil responses, including the oxidative burst. Since the FcgRIIIb/CR3 cooperation occurs via lectin-sacharide-like interaction, the aim of this study was to evaluate whether the allelic polymorphism, NA1 and NA2, could influence the cooperation of FcgRIIIb with CR3 in mediating the oxidative burst of neutrophils. FcgRIIa and FcgRIIIb genotyping analysis were performed by polymerase chain reaction with allelespecific primers and surface expressions of FcgRIIa, FcgRIIIb, CR1 and CR3 on neutrophils were determined by flow cytometry. The FcgRIIIb genotype distribution (n=169) was NA1/NA2 (52.1%), NA2 (27.8%) and NA1 (20.1%). SH gene was found in 11 (6.3%) volunteers from 174 subjects. With respect to the FcgRIIa genotype (n=143), the distribution observed was R131 (41.2%), H/R131 (38.5%) and H (20.3%). Neutrophils were stimulated with immune complexes (IC)-IgG opsonized or not with complement and the oxidative burst... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Neutrofilos, Hematologia, Burst oxidativo, Oxidative burst
Como citar
URBACZEK, Ana Carolina. Burst oxidativo dos neutrófilos humanos: estudo da influência do polimorfismo do receptor para IgG FeyRIIIb na cooperação com os receptores para complemento. 2008. 127 f. Dissertação (mestrado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2008.