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Effects of staphylococcal enterotoxins (SEs) on the mice bone marrow mature granulocytes production and functions

Grant number: 09/16522-0
Support type:Research Grants - Young Investigators Grants
Duration: October 01, 2010 - January 31, 2015
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Ivani Aparecida de Souza
Grantee:Ivani Aparecida de Souza
Home Institution: Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil
Assoc. researchers:Edson Antunes
Associated scholarship(s):12/05561-8 - Effect of staphylococcal enterotoxins type a and b on the adhesion and chemotactic response of mice bone marrow granulocytes, BP.MS

Abstract

The staphylococcal enterotoxins (SEs) are proteins produced and secreted by the gram-positive bacterium Staphylococcus aureus, and are responsible for most of the pathological conditions seen in infections caused by S. aureus, including the pulmonary infections in hospitalar environment. Previous studies carried out in humans have reported a correlation between levels of IgE antibodies to SEs and respiratory diseases exacerbation, including allergic asthma. However, little is known about the mechanisms underlying such inflammatory exacerbation in asthmatic individuals under exposure to SEs. Our recently studies have been showing that staphylococcal enterotoxin type A (SEA) and type B (SEB), given intratracheally to rats and mice, are able to induce a marked increase on mature and immature granulocyte (neutrophil/eosinophil) counts in bone marrow. Thus, the action of SEs on bone marrow can represent an important step on the mechanism by the SEA (or SEB) pre-exposition can exacerbate the allergic pulmonary inflammation in atopic human (BACHERT et al., 2007; ROSSI & MONASTEROLO, 2004) and in animal experimental models (MARIANO et al., 2009). However, little is known about the SEs actions on the production and/or function of bone marrow cells. Therefore, the aim of this study is investigate the role (direct or indirect) of SEA or SEB on the production and function of granulocytes from mice bone marrow. Thus, the following parameters will be investigated in SEA or SEB-mice exposure: 1) Dose and time-course of the modification on bone marrow cell counts after SEA or SEB exposition mice; 2) On the supernatant and cellular suspensions from SEs-treated mice bone marrow we will invastigate the levels of cytokines (GM-CSF, IL-5, IL-4, IL-3 e TNF-a), quemokines (eotaxina, SDF-1±/CXCL12, G-CSF, MIP2/CXCL2 e KC/CXCL1), tachykinins from sensorial fibers (substance P and neurokinin A and the expression of their respective receptors: NK1 and NK2), and nitrite/nitrate (and expression of nitric oxide synthase isoforms: eNOS, bNOS e iNOS); 3) On bone marrow granulocyte (neutrophil and eosinophil) from SEs-treated mice we will invastigate the ability of adhesion and quimiotactic response in vitro and the expression of adhesion molecules involved on the granulocyte mobilization to inflammatory sites. Every parameters above will be also invastigate on bone marrow from naive mice, after in vitro incubation with SEs. Taken in consideration the high number of hospital infections induced by Staphylococcus aureus, and the recent evidences that SEs are the main ethiologic factor for alergic respiratory diseases, the findings from this project can provide advancement on the elucidation of the SEs mechanisms during Staphylococcus aureus pulmonary infections and on the allergic exacerbations by gram-positive bacterial exposition. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERREIRA-DUARTE, ANA P.; PINHEIRO-TORRES, ANELIZE S.; ANHE, GABRIEL F.; CONDINO-NETO, ANTONIO; ANTUNES, EDSON; DESOUZA, IVANI A. MHC Class II Activation and Interferon-gamma Mediate the Inhibition of Neutrophils and Eosinophils by Staphylococcal Enterotoxin Type A (SEA). FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 7, DEC 13 2017. Web of Science Citations: 1.
TAKESHITA, W. M.; GUSHIKEN, V. O.; FERREIRA-DUARTE, A. P.; PINHEIRO-TORRES, A. S.; RONCALHO-BUCK, I. A.; SQUEBOLA-COLA, D. M.; MELLO, G. C.; ANHE, G. F.; ANTUNES, E.; DESOUZA, I. A. Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice. Toxicology and Applied Pharmacology, v. 287, n. 3, p. 267-275, SEP 15 2015. Web of Science Citations: 1.

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