%0 Journal Article
%T Hypoxia modulates human eosinophil function
%A Alon H Nissim Ben Efraim
%A Ron Eliashar
%A Francesca Levi-Schaffer
%J Clinical and Molecular Allergy
%D 2010
%I BioMed Central
%R 10.1186/1476-7961-8-10
%X To characterize eosinophil function and angiogenic potential under hypoxic conditions.Human peripheral blood eosinophils were cultured in normoxic or hypoxic conditions with or without cytokines. Viability and apoptosis were assessed by Annexin V/PI staining. Anti- or pro-apoptotic protein levels, HIF-1¦Á levels and MAPK phosphorylation were analyzed by immunoblot analysis. Angiogenic mediator release was evaluated by ELISA.Hypoxic eosinophils were more viable than normoxic ones after up to three days. In addition in hypoxia, anti-apoptotic Bcl-XL protein levels increased more than pro-apoptotic Bax levels. Hypoxia increased VEGF and IL-8 release. In hypoxic eosinophils high levels of HIF-1¦Á were observed, particularly in the presence of GM-CSF. MAPK, particularly ERK1/2 inhibitors, decreased hypoxia-mediated VEGF release and HIF-1¦Á expression.Eosinophils respond to hypoxia by up-regulation of survival and of some of their pro-angiogenic functions indicating a correlation between eosinophilic inflammation and angiogenesis.Allergic diseases are generally characterized by inflammation, in which tissue infiltration of myeloid cells, mainly eosinophils and Th2 cells, is an important feature [1-5].The microenvironment of injured inflamed tissues is mostly characterized by high concentrations of lactate and reductive metabolites, as well as by low levels of glucose and oxygen [6]. This low oxygen level, or hypoxia, is due to an inadequate blood supply and high consumption of oxygen by the infiltrated cells [7-9].Hypoxic conditions have been shown to profoundly affect a broad range of myeloid cell properties in vitro, e.g., phagocytosis, cell surface marker expression, secretion of cytokines, chemokine receptor levels, adhesion, migration, and cell survival [9]. In addition, hypoxia promotes remodeling and angiogenesis, the sprouting of new blood vessels from pre-existing ones, thus renewing the blood supply and increasing oxygen levels in the tissue [10,11]. Several transc
%U http://www.clinicalmolecularallergy.com/content/8/1/10