Essential roles of endogenous glucocorticoids and TNF/TNFR1 in promoting bone-marrow eosinopoiesis in ovalbumin-sensitized, airway-challenged mice

Masid-de-Brito, Daniela; Xavier−Elsas, Pedro; Luz, Ricardo Alves; Queto, Túlio; Silva, Cássio Luiz Coutinho Almeida da; Lopes, Rodrigo Soares; Vieira, Bruno Marques; Gaspar−Elsas, Maria Ignez C.

doi:10.1016/j.lfs.2013.11.006

Cited by 10 publications

(25 citation statements)

References 26 publications

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“…Priming of bone-marrow in vivo for an increased ex vivo response to IL-5 in bone-marrow culture is a very reproducible effect of allergen challenge [9, 10]. Allergen challenge of sensitized animals in different models has been shown to result in IL-5 [9, 10, 12] and CysLT production [13, 15].…”

Section: Discussionmentioning

confidence: 99%

“…Allergen challenge of sensitized animals in different models has been shown to result in IL-5 [9, 10, 12] and CysLT production [13, 15]. Montelukast, which blocks CysLT actions on eosinopoiesis in vitro [19, 20], acted in vivo to block the primary effect of allergen challenge on the bone-marrow, which is an increased eosinophil count, usually accompanied by priming for increased responses to IL-5 in culture [9, 10]. Hence, it is reasonable to assume that priming involves an effect of CysLT that can be blocked by montelukast and is therefore mediated by CysLT1R.…”

Section: Discussionmentioning

confidence: 99%

“…Data (mean ± SEM) were analyzed by factorial analysis of variance with the Tukey HSD correction for groups of equal size, using Systat for Windows version 4 software from Systat Inc. (Evanston, IL) [10]. For groups of unequal size, the Bonferroni correction was used [9].…”

Section: Methodsmentioning

confidence: 99%

“…In acute eosinophilic inflammation, infiltrating eosinophils eventually die through apoptosis and are cleared by resident macrophages, leading to resolution [7]. By contrast, a sustained increase in bone-marrow eosinophil production ( eosinopoiesis ), as well as prolonged survival in the peripheral inflammatory site, is believed to promote chronic allergic inflammation in humans and mice [8–10]. Furthermore, there is evidence that eosinophil progenitors accumulate in the challenged lungs of sensitized mice, suggesting that extramedullary eosinopoiesis also contributes to the hematological response to allergen exposure [11, 12].…”

Section: Introductionmentioning

confidence: 99%

“…These mechanisms were initially shown to act systemically, because the bone-marrow is not directly exposed to allergen but responds to factors generated in the lungs, which are demonstrable in plasma by a transfer protocol [9]. More recently, TNF- α and corticosterone, a stress hormone released by the adrenal glands, were shown to be required for the increase in eosinopoiesis in response to allergen challenge of sensitized mice [10]. However, neither TNF- α nor corticosterone is eosinophil-selective in their effects, and their production is not restricted to sensitized/challenged animals.…”

Section: Introductionmentioning

confidence: 99%

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Roles of 5-Lipoxygenase and Cysteinyl-Leukotriene Type 1 Receptors in the Hematological Response to Allergen Challenge and Its Prevention by Diethylcarbamazine in a Murine Model of Asthma

Masid-de-Brito

Queto

Gaspar−Elsas

et al. 2014

Mediators of Inflammation

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Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC.

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