Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species

Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species

Autor Fernandes, Maria da Luz Autor UNIFESP Google Scholar
Mendes, Marialice Erdelyi Autor UNIFESP Google Scholar
Brunialti, Milena Karina Coló Autor UNIFESP Google Scholar
Salomão, Reinaldo Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS) was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR)2/6 agonist) and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist). LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity.
Palavra-chave IL-6
ROS
Phagocytosis
MALP-2
Flagellin
LPS tolerance
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Número do financiamento FAPESP: 2006/58744-1
Data de publicação 2010-09-01
Publicado em Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 43, n. 9, p. 860-868, 2010.
ISSN 0100-879X (Sherpa/Romeo, fator de impacto)
Publicador Associação Brasileira de Divulgação Científica
Extensão 860-868
Fonte http://dx.doi.org/10.1590/S0100-879X2010007500081
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000283262800008
SciELO S0100-879X2010000900008 (estatísticas na SciELO)
Endereço permanente http://repositorio.unifesp.br/handle/11600/5906

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