Variable Airway Responsiveness to Inhaled Lipopolysaccharide

Kline, Joel N.; Cowden, John D.; Hunninghake, Gary W.; Schutte, Brian C.; Watt, Janet L.; Wohlford‐Lenane, Christine L.; Powers, Linda S.; Jones, Michael P.; Schwartz, David A.

doi:10.1164/ajrccm.160.1.9808144

Cited by 204 publications

(163 citation statements)

References 32 publications

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“…The involvement of TLR4 signaling in neutrophil recruitment in response to aerosol LPS was shown by others in C3H/ HeJ endotoxin resistant mice bearing a point mutation of the tlr4 gene and in C57BL/10ScNCr mice with a complete deletion of the tlr4 gene (37) and recently in TLR4-deficient mice (42)(43)(44). In humans, mutations affecting the extracellular domain of the TLR4 receptor were shown to be associated with blunted response to inhaled LPS (6,7). However, the role of TLR4-signaling in direct LPS-induced bronchoconstriction was not investigated before in mice.…”

Section: Discussionmentioning

confidence: 88%

“…Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma (2)(3)(4)(5). Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to proteinrich fluid leak in the alveolar space (6,7). The majority of these pathologic features of human airway inflammation have also been observed in experimental lung injury models.…”

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confidence: 99%

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Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin

Noulin

Quesniaux

Schnyder‐Candrian

et al. 2005

The Journal of Immunology

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Inhaled endotoxin induces an inflammatory response that contributes to the development and severity of asthma and other forms of airway disease. Here, we show that inhaled endotoxin-induced acute bronchoconstriction, TNF, IL-12p40, and KC production, protein leak, and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecule MyD88. Bronchoconstriction, inflammation, and protein leak are normal in Toll/IL-1R domain-containing adaptor inducing IFN-β-deficient mice. MyD88 is involved in TLR, but also in IL-1R-associated kinase 1-mediated IL-1R and -18R signaling. We exclude a role for IL-1 and IL-18 pathways in this response, as IL-1R1 and caspase-1 (ICE)-deficient mice develop lung inflammation while TLR4-deficient mice are unresponsive to inhaled LPS. Significantly, using bone marrow chimera, we demonstrate that both hemopoietic and resident cells are necessary for a full MyD88-dependent response to inhaled endotoxin; bronchoconstriction depends on resident cells while cytokine secretion is mediated by hemopoietic cells.

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin

Noulin

Quesniaux

Schnyder‐Candrian

et al. 2005

The Journal of Immunology

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“…Inflammatory responses to inhaled endotoxin have been studied in both humans (2,(32)(33)(34) and mice (35)(36)(37)(38). In general, inhalation or nasal aspiration of endotoxin by mice induces similar host responses and changes (35,39), and these reflect human airway responsiveness (33).…”

Section: Discussionmentioning

confidence: 99%

MD-2–Dependent Pulmonary Immune Responses to Inhaled Lipooligosaccharides

Hađina¹,

Weiss²,

McCray³

et al. 2008

Am J Respir Cell Mol Biol

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Endotoxins represent one of the most potent classes of microbial immunoactive components that can cause pulmonary inflammation. The aim of this study was to compare the inflammatory potency of two types of Neisseria meningitidis endotoxins (lipooligosaccharides) in lungs: wild type (hexaacylated, LOS wt ) and mutant type (pentaacylated, LOS msbB ), and to determine the importance of MD-2 in endotoxin responses in lungs in vivo. Endotoxin-normoresponsive mice (BALB/c) were exposed to selected doses of penta-and hexaacylated lipooligosaccharides (LOS) by nasal aspiration. Cellular and cytokine/chemokine inflammatory responses in bronchoalveolar lavage were measured at 1-, 4-, 8-, 16-, 24-, and 48-hour time points. MD-2-null mice were exposed to one dose of hexaacylated LOS and inflammatory responses were measured after 4 and 24 hours. Inhalation of hexaacylated LOS resulted in strong inflammatory responses, while pentaacylated LOS was much less potent in inducing increases of neutrophils, TNF-a, macrophage inflammatory protein-1a, IL-6, granulocyte colony-stimulating factor, and IL-1b concentration in bronchoalveolar lavage. Similar kinetics of inflammatory responses in lungs were found in both types of endotoxin exposures. Inhalation of hexaacylated LOS in MD-2-null mice resulted in significantly lower numbers of neutrophils in bronchoalveolar lavage than in normoresponsive mice. Markedly lower inflammatory potency of pentaacylated LOS was observed compared with hexaacylated LOS. Hyporesponsiveness in MD-2-null mice after nasal aspiration of wild-type LOS indicate its essential role in airway responsiveness to endotoxin.

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“…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].…”

mentioning

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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Variable Airway Responsiveness to Inhaled Lipopolysaccharide

Cited by 204 publications

References 32 publications

Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin

Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin

MD-2–Dependent Pulmonary Immune Responses to Inhaled Lipooligosaccharides

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

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