BAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes

dc.creatorSoeiro-Pereira, P. V.
dc.creatorFalcai, A.
dc.creatorKubo, C. A.
dc.creatorOliveira-Junior, E. B.
dc.creatorMarques, O. C.
dc.creatorAntunes, E.
dc.creatorCondino-Neto, A.
dc.date2012
dc.date2013-09-19T18:05:54Z
dc.date2016-07-01T15:17:00Z
dc.date2013-09-19T18:05:54Z
dc.date2016-07-01T15:17:00Z
dc.date.accessioned2018-03-29T01:55:33Z
dc.date.available2018-03-29T01:55:33Z
dc.identifierBritish Journal of Pharmacology. Wiley-Blackwell, v.166, n.5, p.1617-1630, 2012
dc.identifier0007-1188
dc.identifierWOS:000305560800012
dc.identifier10.1111/j.1476-5381.2011.01764.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/1821
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/1821
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1308825
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBACKGROUND AND PURPOSE Phagocyte function is critical for host defense against infections. Defects in phagocytic function lead to several primary immunodeficiencies characterized by early onset of recurrent and severe infections. In this work, we further investigated the effects of BAY 41-2272, a soluble guanylate cyclase (sGC) agonist, on the activation of human peripheral blood monocytes (PBM) and THP-1 cells. EXPERIMENTAL APPROACH THP-1 cells and PBM viability was evaluated by methylthiazoletetrazolium assay; reactive oxygen species production by lucigenin chemiluminescence; gene and protein expression of NAPDH oxidase components by qRT-PCR and Western blot analysis, respectively; phagocytosis and microbicidal activity by co-incubation, respectively, with zymosan and Escherichia coli; and cytokine release by elisa. KEY RESULTS BAY 41-2272, compared with the untreated group, increased spreading of monocytes by at least 35%, superoxide production by at least 50%, and gp91PHOX and p67PHOX gene expression 20 to 40 times, in both PBM and THP-1 cells. BAY 41-2272 also augmented phagocytosis of zymosan particles threefold compared with control, doubled microbicidal activity against E. coli and enhanced the release of TNF-a and IL-12p70 by both PBM and THP-1 cells. Finally, by inhibiting sGC with ODQ, we showed that BAY 41-2272-induced superoxide production and phagocytosis is not dependent exclusively on sGC activation. CONCLUSIONS AND IMPLICATIONS In addition to its ability to induce vasorelaxation and its potential application for therapy of vascular diseases, BAY 41-2272 was shown to activate human mononuclear phagocytes. Hence, it is a novel pro-inflammatory drug that may be useful for controlling infections in the immunocompromised host.
dc.description166
dc.description5
dc.description1617
dc.description1630
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherWiley-Blackwell
dc.publisherHoboken
dc.relationBritish Journal of Pharmacology
dc.rightsfechado
dc.sourceWOS
dc.subjectBAY 41-2272
dc.subjectcGMP
dc.subjectNADPH oxidase
dc.subjectgp91PHOX
dc.subjectp67PHOX
dc.subjectmicrobicidal activity
dc.subjectCHRONIC GRANULOMATOUS-DISEASE
dc.subjectCHAIN GENE-EXPRESSION
dc.subjectCYTOCHROME-B HEAVY
dc.subjectNITRIC-OXIDE
dc.subjectINTERFERON-GAMMA
dc.subjectPROTEIN-KINASE
dc.subjectHUMAN NEUTROPHILS
dc.subjectNADPH OXIDASE
dc.subjectBINDING PROTEIN
dc.subjectRAT NEUTROPHILS
dc.titleBAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes
dc.typeArtículos de revistas


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