title: The sickle cell mouse lung: proinflammatory and primed for allergic inflammation.
abstract: Comorbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We used a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal route followed by daily, nose-only OVA-aerosol challenge to induce AAD. The lungs of naive SCD mice showed signs of inflammatory and immune processes: (1) histologic and cytochemical evidence of airway inflammation compared with naive wild-type mice; (2) bronchoalveolar lavage (BAL) fluid contained increased total lymphocytes, %CD8+ T cells, granulocyte-colony stimulating factor, interleukin 5 (IL-5), IL-7, and chemokine (C-X-C motif) ligand (CXCL)1; and (3) lung tissue and hilar lymph node (HLN) had increased CD4+, CD8+, and regulatory T (Treg) cells. Furthermore, SCD mice at AAD demonstrated significant changes compared with the naive state: (1) BAL fluid with increased %CD4+ T cells and Treg cells, lower %CD8+ T cells, and decreased interferon gamma, CXCL10, chemokine (C-C motif) ligand 2, and IL-17; (2) serum with increased OVA-specific immunoglobulin E, IL-6, and IL-13, and decreased IL-1α and CXCL10; (3) no increase in Treg cells in the lung tissue or HLN; and (4) hyporesponsiveness to methacholine challenge. In conclusion, SCD mice have an altered immunologic pulmonary milieu and physiological responsiveness. These findings suggest that the clinical phenotype of AAD in SCD mice differs from that of wild-type mice and that individuals with SCD may also have a unique, divergent phenotype perhaps amenable to a different therapeutic approach.
authors.affiliation: Division of Hematology-Oncology, Lea Center for Hematologic Disorders, Adult Sickle Cell Center, University of Connecticut Health Center, Farmington, Conn. Electronic address: andemariam@uchc.edu.
authors.forename: Biree
authors.initials: B
authors.lastname: Andemariam
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Conn.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Adami
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Conn.
authors.forename: Anurag
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Conn.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: McNamara
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Conn.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Secor
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Conn.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Guernsey
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Conn.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Thrall
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000097:blood / Q000150:complications / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000150:complications / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D057898:Hemizygote; D006967:Hypersensitivity / Q000097:blood / Q000150:complications* / Q000276:immunology*; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000276:immunology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D010047:Ovalbumin
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