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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Fernandes, M. L. [1] ; Mendes, M. E. [1] ; Brunialti, M. K. C. [1] ; Salomao, R. [1]
Total Authors: 4
[1] Univ Fed Sao Paulo, Lab Imunol, EPM, Div Molestias Infecciosas, BR-04039032 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 43, n. 9, p. 860-868, SEP 2010.
Web of Science Citations: 14

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. (AU)

FAPESP's process: 06/58744-1 - Sepsis: integrating basic research and clinical investigation
Grantee:Reinaldo Salomão
Support Opportunities: Research Projects - Thematic Grants