Haptoglobin polymorphism correlated with coronary artery disease

A b s t r a c t I In nt tr ro od du uc ct ti io on n: : Haptoglobin polymorphism has been correlated with disease and some studies have associated the Hp 2 allele with susceptibility to or protection against certain infectious (pulmonary tuberculosis, HIV) and non-infectious (diabetes, coronary artery disease, obesity) diseases. The aim of this study was to verify possible correlations of haptoglobin genotypes and subtypes by comparing coronary artery disease (CAD) patients with blood donors. M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : Haptoglobin genotypes and subtypes were analyzed by DNA amplification with the DraI restriction enzyme, in 125 CAD patients diagnosed by coronary angiography, and 125 blood donors as matched healthy controls. R Re es su ul lt ts s: : The distribution of haptoglobin genotypes was similar in the groups, without significant statistical differences (p = 0.643). The Hp 2 /Hp 2 genotype was more frequent in both the CAD group and blood donors followed by Hp 2 /Hp 1 and Hp 1 /Hp 1 . The allele frequency of Hp 2 was higher than Hp 1 in the groups. The results showed a significant difference (p = 0.002) between the groups regarding haptoglobin subtypes; Hp 2FS /Hp 2FS was prevalent in both groups with the least frequent subtype being Hp 2FF /Hp 2FF for CAD patients and Hp 1F /Hp 1S among blood donors. There was a statistically significant difference (p = 0.027) between the frequencies of the commonest allele subtype, Hp 2FS , and the least common, Hp 2FF . C Co on nc cl lu us si io on ns s: : Unlike blood donors, the Hp 2FF /Hp 2FF haptoglobin subtype was the least frequent among CAD patients, which may implicate this subtype in the development of CAD, a disease with a high mortality rate which consequently reduces the proportion of these individuals in populations. K Ke ey y w wo or rd ds s: : haptoglobin polymorphism, coronary artery disease, blood donors, correlation with disease

Involvement of major components from sporothrix schenckii cell wall in the caspase-1 activation, nitric oxide and cytokines production during experimental sporotrichosis

Sporotrichosis is a chronic infection caused by the dimorphic fungus Sporothrix schenckii, involving all layers of skin and the subcutaneous tissue. The role of innate immune toll-like receptors 2 and 4 in the defense against this fungus has been reported, but so far, there were no studies on the effect of cell wall major components over the cytosolic oligo-merization domain (NOD)-like receptors, important regulators of inflammation and responsible for the maturation of IL-1 beta and IL-18, whose functions are dependents of the caspase-1 activation, that can participate of inflammasome. It was evaluated the percentage of activation of caspase-1, the production of IL-1 beta, IL-18, IL-17, IFN-gamma and nitric oxide in a Balb/c model of S. schenckii infection. It was observed a decreased activity of caspase-1 during the fourth and sixth weeks of infection accompanied by reduced secretion of the cytokines IL-1 beta, IL-18 and IL-17 and high production of nitric oxide. IFN-gamma levels were elevated during the entire time course of infection. This temporal reduction in caspase-1 activity coincides exactly with the reported period of fungal burden associated with a transitory immunosuppression induced by this fungus and detected in similar infection models. These results indicate the importance of interaction between caspase-1, cytokines IL-1 beta and IL-18 in the host defense against S. schenckii infection, suggesting a participation the inflammasome in this response.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Influence of TLR-2 in the immune response in the infection induced by fungus Sporothrix schenckii

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The Predominance of Alternatively Activated Macrophages Following Challenge with Cell Wall Peptide-Polysaccharide After Prior Infection with Sporothrix schenckii

Sporotrichosis is a subcutaneous mycosis that is caused by the dimorphic fungus Sporothrix schenckii. This disease generally occurs within the skin and subcutaneous tissues, causing lesions that can spread through adjacent lymphatic vessels and sometimes leading to systemic diseases in immunocompromised patients. Macrophages are crucial for proper immune responses against a variety of pathogens. Furthermore, macrophages can play different roles in response to different microorganisms and forms of activation, and they can be divided into classic or alternatively activated populations, as also known as M1 and M2 macrophages. M1 cells can lead to tissue injury and contribute to pathogenesis, whereas M2 cells promote angiogenesis, tissue remodeling, and repair. The aim of this study was to investigate the roles of M1 and M2 macrophages in a sporotrichosis model. Toward this end, we performed phenotyping of peritoneal exudate cells and evaluated the concomitant production of several immunomediators, including IL-12, IL-10, TGF-β, nitric oxide, and arginase-I activity, which were stimulated ex vivo with cell wall peptide-polysaccharide. Our results showed the predominance of the M2 macrophage population, indicated by peaks of arginase-I activity as well as IL-10 and TGF-β production during the 6th and 8th weeks after infection. These results were consistent with cellular phenotyping that revealed increases in CD206-positive cells over this period. This is the first report of the participation of M2 macrophages in sporotrichosis infections. © 2013 Springer Science+Business Media Dordrecht