Role of 5-lypoxygenase in the regulation of eosinophilopoiesis
-
1
Universidade Federal do Rio de Janeiro, Brazil
-
2
FIOCRUZ, Brazil
Leukotriene D4, a product of 5-lipoxygenase (5-LO), is a potent stimulator of eosinophilopoiesis in bone-marrow cell culture with IL-5 in BALB/c naïve mice. In sensitized and challenged (S/C) BALB/c mice, a similar upregulation of eosinophilopoiesis is observed in bone-marrow cells cultured with IL-5 alone, raising the issue of 5-LO contribution to this upregulation. Diethylcarbamazine is known as an effective inhibitor of leukotriene synthesis, although its mechanism of action is unclear. We showed that diethylcarbamazine suppresses eosinophilopoiesis in S/C animals, both in vivo and in vitro. We here evaluated the effect of leukotriene synthesis blockade on hematopoiesis in allergic mice, and compared it with diethylcarbamazine effects by analyzing: a) 5-lipoxygenase-deficient mice (ALOX) and wild-type controls (PAS) S/C; b) BALB/c mice S/C pretreated with MK886 (5-lipoxygenase activating protein inhibitor) and controls; c) ALOX and PAS mice S/C pretreated with diethylcarbamazine. We analyzed eosinophil numbers in bone-marrow (freshly collected or cultured with IL-5) and in peritoneal fluid of these mice. Blockade of 5-LO in OVA-challenged BALB/c mice by MK886: a) abolished the challenge-induced increase in bone-marrow eosinophil numbers; b) inhibits challenge-induced eosinophil migration to the peritoneal cavity. In OVA-challenge ALOX mice: a) challenge-induced eosinophil migration into the peritoneal cavity is reduced; b) the challenge-induced increase in bone-marrow eosinophil numbers is abolished. Furthermore, diethylcarbamazine treatment suppressed eosinophilopoiesis in OVA-challenged PAS mice, but not in ALOX mice. These results suggest an important role for 5-LO in challenge-induces hematological changes and in the mechanism of action of diethylcarbamazine on the bone-marrow.
Keywords:
lipoxigenase,
eosinophil,
Bone Marrow,
Diethylcarbamazine,
Hematopoiesis
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Masid-de-Brito
D,
Xavier-Elsas
P,
Luz
R,
Lopes
R,
Pinnola
K,
Ferreira
R and
Gaspar-Elsas
M
(2013). Role of 5-lypoxygenase in the regulation of eosinophilopoiesis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00145
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
10 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Miss. Daniela Masid-de-Brito, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, danimsbt@yahoo.com.br
Dr. Pedro Xavier-Elsas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, pxelsas@yahoo.com.br
Dr. Maria Ignez Gaspar-Elsas, FIOCRUZ, Rio de Janeiro, Brazil, gasparelsas@gmail.com