title: Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS) production.
abstract: Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg) may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature) and respiratory distress (dyspnea) were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios) and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.
authors.affiliation: The Toronto Platelet Immunobiology Group, University of Toronto, Toronto, Ontario, Canada. semplej@smh.ca
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.forename: Jing
authors.initials: J
authors.lastname: Hou
authors.forename: Mark
authors.initials: M
authors.lastname: McVey
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Arata
authors.initials: A
authors.lastname: Tabuchi
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Chai
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000143:Acids; D055371:Acute Lung Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D004487:Edema / Q000150:complications; D006801:Humans; D007035:Hypothermia / Q000150:complications / Q000473:pathology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016019:Survival Analysis; D065227:Transfusion Reaction
chemical_list: D000143:Acids; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016756:Immunoglobulins, Intravenous; D017382:Reactive Oxygen Species