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Immunogenetics ; 65(12): 861-71, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24091988

RESUMEN

The recent burst of duplication and divergence of the bovine PLA2G2D genes is considered typical of immune response genes, and it was recently shown that PLA2G2D is abundantly expressed in mouse leukocytes and acts as an immunosuppressive phospholipase. Analysis of 1,143 Holstein bulls indicated that the four common haplotypes spanning PLA2G2D display copy number variation ranging from 1 to 4 per haploid genome. Association of the fourth haplotype with negative total merit remained significant (P < 0.002) when corrected for population relatedness. We compared the lipase and bactericidal activities of bovine pancreatic PLA2G1B with human PLA2G2A and G2D and bovine PLA2G2D1 and G2D4 proteins, which had been subcloned, expressed, and refolded by us, and the impact of point mutations in the calcium binding site was investigated. All tested phospholipases were ineffective bactericides of Escherichia coli isolated from bovine mastitis. However, in lactating mice treated with E. coli or lipopolysaccharide (LPS), intramammary injection of bovine PLA2G1B relieved visual and histological inflammation and reduced blood levels of infiltrating lactose. Further studies are warranted to determine whether the observed anti-inflammatory effect involves competitive binding of the receptor Pla2r1 which may mimic the LPS resistance effect in Pla2r1-deficient mice.


Asunto(s)
Antiinflamatorios/aislamiento & purificación , Fosfolipasas A2 Grupo IV/aislamiento & purificación , Inflamación/metabolismo , Glándulas Mamarias Humanas/patología , Animales , Antiinflamatorios/farmacología , Bovinos , Escherichia coli/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/inmunología , Fosfolipasas A2 Grupo IV/genética , Fosfolipasas A2 Grupo IV/metabolismo , Fosfolipasas A2 Grupo IV/farmacología , Haplotipos , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Lactosa/sangre , Lipopolisacáridos/farmacología , Lipopolisacáridos/toxicidad , Glándulas Mamarias Humanas/metabolismo , Ratones
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