Toll-like receptor 4 signaling is associated with neutrophil migration impairment and severity of polymicrobial sepsis (2005)
- Authors:
- Autor USP: RUSSO, MOMTCHILO - ICB
- Unidade: ICB
- Assunto: IMUNOLOGIA
- Language: Português
- Abstract: Objetivo: We have showed that experimental severe sepsis is associated with impaired neutrophil recruitment into infectious site and high mortality rate. This phenomenon appears to be mediated by excessive release of proinflammatory chemokines/cytokines and a concomitant increase of nitric oxide derived from inducible nitric oxide synthase. Toll-like receptor 4 (TLR4) is the major recognition receptor for LPS, a component of Gram-negative bacterial cell walls. In the present study we investigated whether TLR4 is involved in the failure of neutrophil migration in mice with polymicrobial sepsis due to cecal ligation and puncture (CLP) or to polymicrobial inoculation (PI), or with Gram-negative infection (GNI). Métodos e Resultados: TLR4-deficient (C3H/HeJ) or TLR4-normal (C3H/HePas) mice were used. Our findings indicate that TLR4-deficient mice presented incapacity to promote neutrophil recruitment to infectious site after a sub-lethal GNI (C3H/HeJ: 0.4±0.1; C3H/HePas: 5.8±0.8 cellsx106/cavity), resulting in high mortality (100%). However, TLR4 signaling is not essential to display neutrophil migration in sub-lethal polymicrobial sepsis induced by both CLP and PI models (CLP= C3H/HeJ: 11.2±1.3; C3H/HePas:14.9±1.9/ PI= C3H/HeJ:4.4±0.9; C3H/HePas:5.0±1.1 cellsx106/cavity), but surprisingly, it is crucial to establish the impairment of neutrophil migration in lethal polymicrobial sepsis.) We observed that differently from TLR4-normal, theTLR4-deficient mice underwent to lethal CLP or PI did not present failure of neutrophil migration to infectious focus (CLP= C3H/HeJ:10.2±1.2; C3H/HePas:2.6±0.8/ PI= C3H/HeJ: 6.2±0.4; C3H/HePas: 1.6±0.2 cellsx106/cavity). As consequence they present reduced bacteremia (53%) and systemic inflammation, since circulating levels of TNF-_, MIP-2 and lung neutrophil sequestration were diminished 63%, 52% and 51% respectively, resulting in enhanced survival rate (45%). Conclusões: Our results show that TLR4 signaling is detrimental to polymicrobial sepsis, while it is critical to the control of a local Gram-negative infection. Thus, we envisage that the development of specific TLR4 antagonists might have potential therapeutic value for the treatment of polymicrobial sepsis
- Imprenta:
- Publisher: Federação de Sociedades de Biologia Experimental
- Publisher place: Águas de Lindóia, São Paulo
- Date published: 2005
- Source:
- Título do periódico: Resumos
- Conference titles: Reunião Anual da Federação de Sociedades de Biologia Experimental, FeSBE
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ABNT
ALVES-FILHO, J. C. et al. Toll-like receptor 4 signaling is associated with neutrophil migration impairment and severity of polymicrobial sepsis. 2005, Anais.. Águas de Lindóia, São Paulo: Federação de Sociedades de Biologia Experimental, 2005. . Acesso em: 18 set. 2024. -
APA
Alves-Filho, J. C., Moreno, S. E., Freitas, A., Spiller, F., Russo, M., & Cunha, F. de Q. (2005). Toll-like receptor 4 signaling is associated with neutrophil migration impairment and severity of polymicrobial sepsis. In Resumos. Águas de Lindóia, São Paulo: Federação de Sociedades de Biologia Experimental. -
NLM
Alves-Filho JC, Moreno SE, Freitas A, Spiller F, Russo M, Cunha F de Q. Toll-like receptor 4 signaling is associated with neutrophil migration impairment and severity of polymicrobial sepsis. Resumos. 2005 ;[citado 2024 set. 18 ] -
Vancouver
Alves-Filho JC, Moreno SE, Freitas A, Spiller F, Russo M, Cunha F de Q. Toll-like receptor 4 signaling is associated with neutrophil migration impairment and severity of polymicrobial sepsis. Resumos. 2005 ;[citado 2024 set. 18 ] - Participação de anticorpos de diferentes isotipos na alteração de preferência ao sabor induzida imunologicamente em camundongos: um estudo por meio da tolerância oral
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