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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jandl, K; Stacher, E; Bálint, Z; Sturm, EM; Maric, J; Peinhaupt, M; Luschnig, P; Aringer, I; Fauland, A; Konya, V; Dahlen, SE; Wheelock, CE; Kratky, D; Olschewski, A; Marsche, G; Schuligoi, R; Heinemann, A.
Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung.
J Allergy Clin Immunol. 2016; 137(3):833-843
Doi: 10.1016/j.jaci.2015.11.012
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- Führende Autor*innen der Med Uni Graz
- Heinemann Akos
- Jandl Katharina
- Co-Autor*innen der Med Uni Graz
- Aringer Ida
- Balint Zoltan
- Böhm Eva
- Konya Viktoria
- Kratky Dagmar
- Luschnig Petra
- Maric Jovana
- Marsche Gunther
- Olschewski Andrea
- Peinhaupt Miriam
- Schuligoi Rufina
- Stacher-Priehse Elvira
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- Abstract:
- Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor-homologous molecule expressed on T(H)2 cells) in regulating macrophages have not been elucidated to date. We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. In vitro studies, including migration, Ca(2+) flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca(2+) flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (Keywords)
- D-type prostanoid receptor 1
- D-type prostanoid receptor 2/chemoattractant receptor-homologous molecule expressed on T(H)2 cells
- prostaglandin D-2
- hematopoietic prostaglandin D synthase
- macrophages
- pulmonary inflammation
- neutrophils