title: CCL11 elicits secretion of RNases from mouse eosinophils and their cell-free granules.
abstract: Rapid secretion of eosinophil-associated RNases (EARs), such as the human eosinophilic cationic protein (ECP), from intracellular granules is central to the role of eosinophils in allergic diseases and host immunity. Our knowledge regarding allergic inflammation has advanced based on mouse experimental models. However, unlike human eosinophils, capacities of mouse eosinophils to secrete granule proteins have been controversial. To study mechanisms of mouse eosinophil secretion and EAR release, we combined an RNase assay of mouse EARs with ultrastructural studies. In vitro, mouse eosinophils stimulated with the chemokine eotaxin-1 (CCL11) secreted enzymatically active EARs (EC(50) 5 nM) by piecemeal degranulation. In vivo, in a mouse model of allergic airway inflammation, increased airway eosinophil infiltration (24-fold) correlated with secretion of active RNases (3-fold). Moreover, we found that eosinophilic inflammation in mice can involve eosinophil cytolysis and release of cell-free granules. Cell-free mouse eosinophil granules expressed functional CCR3 receptors and secreted their granule proteins, including EAR and eosinophil peroxidase in response to CCL11. Collectively, these data demonstrate chemokine-dependent secretion of EARs from both intact mouse eosinophils and their cell-free granules, findings pertinent to understanding the pathogenesis of eosinophil-associated diseases, in which EARs are key factors.
authors.affiliation: Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Revital
authors.initials: R
authors.lastname: Shamri
authors.forename: Rossana C N
authors.initials: RC
authors.lastname: Melo
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Young
authors.forename: Maytal
authors.initials: M
authors.lastname: Bivas-Benita
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Xenakis
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Spencer
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D000818:Animals; D002474:Cell-Free System; D054413:Chemokine CCL11 / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D012260:Ribonucleases / Q000378:metabolism*
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D012260:Ribonucleases