Respiratory Burst: Role in Signal Transduction in Alveolar Macrophages

Gwinn, Maureen R.; Vallyathan, Val

doi:10.1080/15287390500196081

Cited by 128 publications

(98 citation statements)

References 76 publications

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“…[42][43][44] Under these stimuli (IFN-g or LPS), we detected increased levels of NBS1. In Nbs1 ΔB/ΔB macrophages, this stimulation led to increased DNA damage that could be strongly reduced by the addition of N-acetyl-L-cysteine, indicating that the MRE11 complex was important for suppressing ROS-induced DNA damage ( Figure 1D).…”

Section: Discussionmentioning

confidence: 77%

NBS1 is required for macrophage homeostasis and functional activity in mice

Pereira-Lopes

Tur

Calatayud-Subias

et al. 2015

Blood

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• Nbs1 is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response.• In mice with a hypomorphic allele of Nbs1, macrophages exhibit increased senescence and abnormal proliferation and inflammatory responses. , macrophage activation-induced ROS caused increased levels of DNA damage that were associated with defects in proliferation, delayed differentiation, and increased senescence. Furthermore, upon stimulation, Nbs1 ΔB/ΔB macrophages exhibited increased expression of proinflammatory cytokines. In the in vivo 2,4-dinitrofluorobenezene model of inflammation, Nbs1 ΔB/ΔB animals showed increased weight and ear thickness. By using the sterile inflammation by zymosan injection, we found that macrophage proliferation was drastically decreased in the peritoneal cavity of Nbs1 ΔB/ΔB mice. Our findings show that NBS1 is crucial for macrophage function during normal aging. These results have implications for understanding the immune defects observed in patients with NBS and related disorders. (Blood. 2015;126(22):2502-2510

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Section: Discussionmentioning

confidence: 77%

NBS1 is required for macrophage homeostasis and functional activity in mice

Pereira-Lopes

Tur

Calatayud-Subias

et al. 2015

Blood

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“…Cross-talk between lung epithelial cells and alveolar macrophages is known to inhibit the latter's inflammatory properties [43,44]. Although alveolar macrophages are quiescent under steady-state conditions, they can be activated by extrinsic and intrinsic stimuli and then participate in phagocytosis, bacterial killing and tissue wound healing [45,46]. As seen in Fig.…”

Section: Discussionmentioning

confidence: 99%

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

et al. 2009

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Bacterial products (such as endotoxins and flagellin) trigger innate immune responses through TLRs. Flagellin-induced signalling involves TLR5 and MyD88 and, according to some reports, TLR4. Whereas epithelial and dendritic cells are stimulated by flagellin in vitro, the cell contribution to the in vivo response is still unclear. Here, we studied the respective roles of radioresistant and radiosensitive cells in flagellin-induced airway inflammation in mice. We found that i.n. delivery of flagellin elicits a transient change in respiratory function and an acute, pro-inflammatory response in the lungs, characterized by TLR5-and MyD88-dependent chemokine secretion and neutrophil recruitment. In contrast, TLR4, CD14 and TRIF were not essential for flagellin-mediated responses, indicating that TLR4 does not cooperate with TLR5 in the lungs. Respiratory function, chemokine secretion and airway infiltration by neutrophils were dependent on radioresistant, TLR5-expressing cells. Furthermore, lung haematopoietic cells also responded to flagellin by activating TNF-a production. We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5-dependent signalling in response to flagellin and thus triggering the lung's innate immune responses.Key words: Chemokine . Epithelium . Flagellin . Lung inflammation . TLR5 IntroductionUpon challenge with respiratory pathogens, the airways rapidly develop a pro-inflammatory response initiated by environmental agents including microbe-associated molecular patterns such as Gram-negative bacteria LPS or endotoxins. This proinflammatory reaction plays an important role in the innate defense against respiratory pathogens [1,2]. Physiological changes induced by endotoxin inhalation include pulmonary Ã These authors contributed equally to this work. Eur. J. Immunol. 2009. 39: 1587-1596 DOI 10.1002 Innate immunity 1587 function and bronchoconstriction, cytokine and chemokine production, PMN recruitment, increased permeability of the alveolar epithelium and the associated endothelium [3][4][5][6]. TLR4 [7], together with MD-2, LPS-binding protein and CD14 detect endotoxins and play a critical role in the initiation of the pulmonary response to systemic and mucosal endotoxin administration [5,[8][9][10]. The pulmonary inflammation to endotoxin involves TLR4 signalling in both the parenchyma cells like endothelial and epithelial cells and the haematopoietic cells, i.e. monocytes, dendritic cells and neutrophils [11]. In addition, TLR4 signalling contributes to the development and progression of chronic respiratory disease including asthma [12][13][14][15][16].Flagellin is the major constituent of flagella from Gramnegative and Gram-positive bacteria. TLR5 has been identified as the main pattern recognition receptor required for flagellinmediated immune signalling [17]. TLR5 signalling depends on MyD88 and results in activation of MAPK, nuclear translocation of NF-kB and production of various pro-inflammatory cytokines and chemokines [18]. Moreover, a previous ...

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“…Studies on the signal transduction mechanism of macrophage activation have indicated that stimuli, such as LPS or IL-4, trigger the mitogenactivated protein kinase (MAPK) and phosphoinositol-3-kinase (PI3K) signaling pathways [20,21] . MAPK pathway positively regulated the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6 etc), whereas PI3K pathway conversely inhibits MAPK pathway activation and induced anti-inflammatory cytokines (IL-10 etc) [22,23] .…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response

et al. 2010

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Aim: To investigate the immunomodulatory effects of andrographolide on both innate and adaptive immune responses. Methods: Andrographolide (10 µg/mL in vitro or 1 mg/kg in vivo) was used to modulate LPS-induced classical activated (M1) or IL-4-induced alternative activated (M2) macrophages in vitro and humor immune response to HBsAg in vivo. Cytokine gene expression profile (M1 vs M2) was measured by real-time PCR, IL-12/IL-10 level was detected by ELISA, and surface antigen expression was evaluated by flow cytometry, whereas phosphorylation level of ERK 1/2 and AKT was determined by Western blot. The level of anti-HBs antibodies in HBsAg immunized mice was detected by ELISA, and the number of HBsAg specific IL-4-producing splenocyte was enumerated by ELISPOT. Results: Andrographolide treatment in vitro attenuated either LPS or IL-4 induced macrophage activation, inhibited both M1 and M2 cytokines expression and decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). Andrographolide down-regulated the expression of mannose receptor (CD206) in IL-4 induced macrophages and major histocompability complex/costimulatory molecules (MHC I, CD40, CD80, CD86) in LPS-induced macrophages. Correspondingly, anti-HBs antibody production and the number of IL-4-producing splenocytes were reduced by in vivo administration of andrographolide. Reduced phosphorylation levels of ERK1/2 and AKT were observed in macrophages treated with andrographolide. Conclusion: Andrographolide can modulate the innate and adaptive immune responses by regulating macrophage phenotypic polarization and Ag-specific antibody production. MAPK and PI3K signaling pathways may participate in the mechanisms of andrographolide regulating macrophage activation and polarization.

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Respiratory Burst: Role in Signal Transduction in Alveolar Macrophages

Cited by 128 publications

References 76 publications

NBS1 is required for macrophage homeostasis and functional activity in mice

NBS1 is required for macrophage homeostasis and functional activity in mice

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response

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