title: Inhaled corticosteroids increase siglec-5/14 expression in sputum cells of COPD patients.
abstract: Recent studies show that several Siglec receptors, such as Siglec-8 and Siglec-14, may be important therapeutic targets in asthma and COPD. Siglecs are a family of lectins belonging to the immunoglobulin superfamily and recognize sialic acid residues of glycoproteins. Most of Siglecs have intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIM), implicating them in the suppression of immunoreceptor signaling. Siglec-5/14 may be involved in the negative regulation of innate immune responses. The aim of this study was to analyze Siglec-5/14 expression in induced sputum cells of COPD patients in the following treatment combinations: (1) a long-acting beta2-agonist, formoterol; (2) formoterol combined with a long-acting antimuscarinic agent, tiotropium; and (3) formoterol combined with an inhaled corticosteroid or formoterol combined with tiotropium and with an inhaled corticosteroid. Siglec expression was assessed in sputum cells by flow cytometry using a specific monoclonal antibody. Double staining of cells indicated that Siglec-5/14 is expressed in monocyte/macrophages and neutrophils, but not in lymphocytes. Siglec-5/14 expression was significantly higher in patients receiving combined therapy including inhaled corticosteroids compared with patients taking only formoterol or formoterol + tiotropium. Our results suggest that inhaled corticosteroids may exert beneficial or negative effects, depending on the patients' phenotype, through increased immunosuppressive Siglec-5 or immunoactivatory Siglec-14 receptors, respectively.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Bialystok, 15A Waszyngtona St., Bialystok, Poland, pwielgat@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Wielgat
authors.forename: R M
authors.initials: RM
authors.lastname: Mroz
authors.forename: A
authors.initials: A
authors.lastname: Stasiak-Barmuta
authors.forename: P
authors.initials: P
authors.lastname: Szepiel
authors.forename: E
authors.initials: E
authors.lastname: Chyczewska
authors.forename: J J
authors.initials: JJ
authors.lastname: Braszko
authors.forename: A
authors.initials: A
authors.lastname: Holownia
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use; D002469:Cell Separation; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000627:therapeutic use*; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D037102:Lectins / Q000819:agonists / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000235:genetics*; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D013183:Sputum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000069447:Tiotropium Bromide
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004983:Ethanolamines; D037102:Lectins; D011956:Receptors, Cell Surface; C514213:SIGLEC14 protein, human; C114531:SIGLEC5 protein, human; D012602:Scopolamine Derivatives; D019819:Budesonide; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide