title: IL-5 induces suspended eosinophils to undergo unique global reorganization associated with priming.
abstract: The experiments described herein define a unique program of polarization of suspended human eosinophils stimulated with IL-5 family cytokines. We found that eosinophil granules and the nucleus move in opposite directions to form, respectively, a granular compartment and the nucleopod, a specialized uropod occupied by the nucleus and covered with adhesion receptors, including P-selectin glycoprotein ligand-1, CD44, and activated αMβ2 integrin. Ligated IL-5 family receptors localize specifically at the tip of the nucleopod in proximity to downstream signaling partners Janus tyrosine kinase 2, signal transducer and activator of transcription-1 and -5, and extracellular signal-regulated kinase. Microscopy and effects of cytochalasin B and nocodazole indicate that remodeling of filamentous actin and reorientation of the microtubule network are required for eosinophil polarization and nucleopod formation. IL-5 induces persistent polarization and extracellular signal-regulated kinase redistribution that are associated with eosinophil priming, a robust response on subsequent stimulation with N-formyl-methionyl-leucyl-phenylalanine. Global reorganization of cytoskeleton, organelles, adhesion receptors, and signaling molecules likely facilitates vascular arrest, extravasation, migration, granule release, and survival of eosinophils entering inflamed tissues from the bloodstream.
authors.affiliation: Departments of 1 Biomolecular Chemistry and.
authors.forename: Shih-Tsung
authors.initials: ST
authors.lastname: Han
authors.forename: Deane F
authors.initials: DF
authors.lastname: Mosher
mesh_terms: D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape; D048429:Cell Size; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015848:Interleukin-5; D016177:Macrophage-1 Antigen; D050791:STAT Transcription Factors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D053612:Janus Kinases; D048049:Extracellular Signal-Regulated MAP Kinases