title: Recombinant human mannose-binding lectin dampens human alveolar macrophage inflammatory responses to influenza A virus in vitro.
abstract: IAV pneumonia remains a serious global health problem, and preventative and therapeutic strategies remain limited. AM are critical effector cells in the control of influenza, impairing IAV replication, promoting IAV clearance, and promoting efferocytosis and resolution of lung inflammation. MBL, an innate immune pattern recognition molecule, present in the lungs, binds IAV, and plasma MBL deficiency is associated with increased susceptibility to IAV, although the mechanism remains incompletely understood, and the influence of MBL on the IAV-AM interaction has not been established. In the current study, focusing on human macrophages (U937 cell line and clinically relevant human AM), data demonstrated that unopsonized IAV is readily internalized, induced release of TNF and ROS, and promoted macrophage apoptosis. In contrast, IAV, opsonized with rhMBL, reduced IAV uptake and macrophage apoptosis and dramatically reduced TNF release and ROS. Macrophage host-defense responses were reduced further in the presence of MASPs. Taken together, these data support the concept that rhMBL may serve a protective innate host response and a critical biological response modifier function by limiting AM inflammation, oxidative injury, and AM apoptosis, which may allow effective IAV clearance while limiting collateral damage to vital organs, such as the lungs.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.|Division of Pulmonary Medicine, Department of Pediatrics, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nelson
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Departments of Medicine and Pathology, Boston University School of Medicine and the Department of Medicine, Boston City Hospital, Boston, Massachusetts, USA; and.
authors.forename: Mitchell
authors.initials: M
authors.lastname: White
authors.affiliation: Departments of Medicine and Pathology, Boston University School of Medicine and the Department of Medicine, Boston City Hospital, Boston, Massachusetts, USA; and.
authors.forename: Kevan
authors.initials: K
authors.lastname: Hartshorn
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.|Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: T Bernard
authors.initials: TB
authors.lastname: Kinane
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Anandaiah
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA; hkoziel@bidmc.harvard.edu.
authors.forename: Henry
authors.initials: H
authors.lastname: Koziel
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D020298:U937 Cells
chemical_list: D037601:Mannose-Binding Lectin; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: C-type lecin; TNF; apoptosis; biological response modifier; innate immunity; respiratory burst