Mobilization with granulocyte colony-stimulating factor blocks medullar erythropoiesis by depleting F4/80(+)VCAM1(+)CD169(+)ER-HR3(+)Ly6G(+) erythroid island macrophages in the mouse
EXPERIMENTAL HEMATOLOGY
Authors: Jacobsen, Rebecca N.; Forristal, Catherine E.; Raggatt, Liza J.; Nowlan, Bianca; Barbier, Valerie; Kaur, Simranpreet; van Rooijen, Nico; Winkler, Ingrid G.; Pettit, Allison R.; Levesque, Jean-Pierre
Abstract
Similarly to other tissues, the bone marrow contains subsets of resident tissue macrophages, which are essential to maintain bone formation, functional hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering with the HSC niche-supportive function of BM resident macrophages. Because bone marrow macrophages are key to both maintenance of HSC within their niche and erythropoiesis, we investigated the effect of mobilizing doses of G-CSF on erythropoiesis in mice. We now report that G-CSF blocks medullar erythropoiesis by depleting the erythroid island macrophages we identified as co-expressing F4/80, vascular cell adhesion molecule-1, CD169, Ly-6G, and the ER-HR3 erythroid island macrophage antigen. Both broad macrophage depletion, achieved by injecting clodronate-loaded liposomes, and selective depletion of CD169(+) macrophages, also concomitantly depleted F4/80(+)VCAM1(+)CD169(+)ER-HR3(+)Ly-6G(+) erythroid island macrophages and blocked erythropoiesis. This more precise phenotypic definition of erythroid island macrophages will enable studies on their biology and function in normal settings and on diseases associated with anemia. Finally, this study further illustrates that macrophages are a potent relay of innate immunity and inflammation on bone, hematopoietic, and erythropoietic maintenance. Agents that affect these macrophages, such as G-CSF, are likely to affect these three processes concomitantly. (C) 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.
A cold water extract of Fucus vesiculosus inhibits lipopolysaccharide (LPS) induced pro-inflammatory responses in the porcine colon ex-vivo model
INNOVATIVE FOOD SCIENCE & EMERGING TECHNOLOGIES
Authors: Bahar, Bojlul; O'Doherty, John V.; Smyth, Thomas J.; Ahmed, Albin M.; Sweeney, Torres
Abstract
The objectives of this experiment were to compare the in-vitro anti-inflammatory activity of crude extracts (cold water (CWE), hot water and 80% ethanol extract) of F. vesiculosus and to predict the key molecular targets of the extract with most anti-inflammatory activity in-vitro. In TNF-alpha. challenged Caco-2 cells, of the three crude extracts, the CWE exhibited maximum inhibition of IL-8 production. In the ex-vivo challenged porcine colonic tissue, CWE inhibited the expression (>2 fold) of inflammatory mediators (PTGS2, C5, LYZ), cytokines (IL17A, IL8), chemokines (CCL2, CXCL2, CXCL10, CXCL11), cell adhesion molecules (ICAM1, VCAM1), toll like receptors (TLR4, TLR7) and components of NF-kappa B (NFKB1, RELB), MAPIC (MAP3K8) and AP-1 (CJUN) pathways. The gene expression analysis suggest that the CWE does contain immunomodulatory bioactive compound/s that mediated through the interferon regulatory system 2, TNF-alpha inducing protein 3 and TNF-a receptor 2 and thus has potential application for human and animal health. (C) 2016 Elsevier Ltd. All rights reserved.