Constitutive and Cytokine-Stimulated Expression of Eotaxin by Human Airway Smooth Muscle Cells

Ghaffar, Omar; Hamid, Qutayba; Renzi, Paolo; Allakhverdi, Zoulfia; Molet, Sophie; Hogg, James C.; Shore, Stephanie A.; Luster, Andrew D.; Lamkhioued, Bouchaïb

doi:10.1164/ajrccm.159.6.9805039

Cited by 176 publications

(131 citation statements)

References 47 publications

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“…Our results suggest that eotaxin͞CCR3 is largely required for this final migratory process. Anatomically, the subendothelial space contains smooth muscle cells and fibroblasts, both cell sources of eotaxin (34,35). It is possible that these cells provide the chemokine gradient that enables cell migration through the vessel wall.…”

Section: Discussionmentioning

confidence: 99%

The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness

Humbles

Liu

Friend

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

357

277

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CCR3 is a chemokine receptor initially thought specific to eosinophils but subsequently identified on TH2 cell subsets, basophils, mast cells, neural tissue, and some epithelia. Because of the prominent role of these cells in allergic disease, including asthma, we generated mice deficient in CCR3 to determine its contribution in a model of allergic airway disease. Here we show that CCR3 is important for the basal trafficking of eosinophils to the intestinal mucosa but not the lung. In contrast, CCR3 disruption significantly curtails eosinophil recruitment to the lung after allergen challenge, with the majority of the eosinophils being arrested in the subendothelial space. Further, a role for CCR3 in mast cell homing has been identified; after sensitization and allergen challenge, we find increased numbers of intraepithelial mast cells in the trachea of knockout mice. Physiologically, we find that the net result of these complex cell fates after sensitization and allergen challenge is a paradoxical increase in airway responsiveness to cholinergic stimulation. These data underscore a more complex role for CCR3 in allergic disease than was anticipated.

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Section: Discussionmentioning

confidence: 99%

The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness

Humbles

Liu

Friend

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

357

277

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“…5-oxo-ETE seems to be an intermediate chemoattractant as it down-regulates the migration of eosinophils to PGD 2 , but enhances their chemotaxis to eotaxin. By doing so, 5-oxo-ETE might divert the migrating eosinophils from the source of PGD 2 (e.g., mast cells) and further accelerate them towards a third chemoattractant, eotaxin, released from end-point targets, such as smooth muscle cells or the epithelium [39][40][41]. Hence, eotaxin could serve as an end-point chemoattractant also causing degranulation of eosinophils [30].…”

Section: Discussionmentioning

confidence: 99%

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

et al. 2006

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Several chemoattractants can regulate the recruitment of eosinophils to sites of inflammation, but the hierarchy among them is unknown. We observed here that eosinophil chemotaxis towards eotaxin or 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) was amplified up to sixfold in the presence of prostaglandin (PG) D 2 . This effect was only seen in eosinophils, and not in neutrophils or basophils. Pretreatment with the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) antagonist ramatroban prevented the PGD 2 enhancement of eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration of eosinophils towards PGD 2 . 5-oxo-ETE enhanced the chemotaxis to eotaxin, while eotaxin had no effect on 5-oxo-ETE-induced migration. 5-oxo-ETE induced the phosphorylation of p38 mitogenactivated protein kinase, and inhibition of p38 mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE on the chemotaxis to PGD 2 from inhibition to enhancement. The presence of blood or plasma markedly decreased the sensitivity of eosinophils to eotaxin or 5-oxo-ETE, while responses to PGD 2 were unaltered. In conclusion, PGD 2 might be an initial chemoattractant, since it maintains its potency in the circulation and augments the responsiveness of eosinophils to other chemoattractants. In contrast, eotaxin seems to be an end-point chemoattractant, since it has reduced efficacy in blood and is capable of down-modulating eosinophil responsiveness to other chemoattractants. IntroductionAccumulation of eosinophils at sites of allergic reactions, such as eczema or asthma, is associated with tissue injury and lung dysfunction [1]. It has been shown recently that asthmatic patients that received treatment based on eosinophil counts in sputum had significantly fewer severe asthma exacerbations than patients treated according to standard management therapy [2]. Moreover, genetically modified mice lacking eosinophils are protected against allergen-induced lung injury and asthma [3,4].Although several chemoattractants can mediate eosinophil recruitment, none of them could be identified so far as a predominating factor governing eosinophil infiltration, suggesting a co-operative action of multiple chemoattractants in disease. Among these are the CC-chemokines, such as eotaxin, RANTES, or MCP-4 acting through the chemokine receptor CCR3 [5,6]. Prostaglandin (PG) D 2 , a major mast cell mediator released during the allergic response [7] might be of particular importance, since PGD 2 is capable of inducing the chemotaxis of eosinophils, basophils and Th2-type * These authors contributed equally to this study. T cells via a novel receptor, chemoattractant receptorhomologous molecule expressed on TH2 cells (CRTH2) [8,9]. Besides chemotaxis, we have shown that activation of CRTH2 also causes eosinophil respiratory burst and the release of eosinophils from the bone marrow [10]. In vivo, PGD 2 can induce pulmonary eosinophilia [11], and a significant contribution of PGD 2 to the late phase allergi...

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“…The T-helper (Th)-2 T-cell derived cytokines, IL-4, IL-10 and IL-13, as well as dexamethasone inhibited RANTES mRNA and protein expression. The more selective eosinophil chemoattractant, eotaxin, is also expressed in human airway smooth muscle cells stimulated by IL-1b or TNFa [31,32]. Both IL-1b and TNFa-induced release of eotaxin was not inhibited by corticosteroids, in contrast to the release of RANTES [31].…”

Section: Chemokinesmentioning

confidence: 97%

“…There is some limited data. RAN-TES expression has been observed in airway smooth muscle cells in airway bronchial biopsies from healthy volunteers as well as from asthmatic subjects [26], while eotaxin immunoreactivity is reported in airway smooth muscle of airways from patients with asthma, with weaker staining in those from healthy volunteers [32], and of airways from guinea-pigs following allergen challenge [82]. Therefore, the production of chemokines in the airway smooth muscle may allow a gradient of chemotaxis to exist between the microvasculature and the airway smooth muscle, allowing T-cells, eosinophils, neutrophils, and monocytes to accumulate around smooth muscle cells.…”

Section: Effects Of Inflammatory Factors On Airway Smooth Muscle Contmentioning

confidence: 99%

“…Both IL-1b and TNFa-induced release of eotaxin was not inhibited by corticosteroids, in contrast to the release of RANTES [31]. The eosinophil chemoattractant activity of stimulated airway smooth muscle supernatants appears to be predominantly accounted for by RANTES and eotaxin [30,32]. Other C-C chemokines that are released include MCP-1, -2 and -3 from airway smooth muscle cells stimulated with a mixture of IL-1b, TNFa and IFNc, effects inhibited by dexamethasone but not by the Th2 cytokines, IL-4, IL-10 and IL-13 [33,34].…”

Section: Chemokinesmentioning

confidence: 99%

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Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Chung

2000

Eur Respir J

131

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In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro‐inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T‐cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro‐activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.

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Constitutive and Cytokine-Stimulated Expression of Eotaxin by Human Airway Smooth Muscle Cells

Cited by 176 publications

References 47 publications

The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness

The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

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