| 1. |
- Crow, Andrew R., et al.
(författare)
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Treating murine inflammatory diseases with an anti-erythrocyte antibody
- 2019
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 11:506
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of autoimmune and inflammatory diseases typically involves immune suppression. In an opposite strategy, we show that administration of the highly inflammatory erythrocyte-specific antibody Ter119 into mice remodels the monocyte cellular landscape, leading to resolution of inflammatory disease. Ter119 with intact Fc function was unexpectedly therapeutic in the K/BxN serum transfer model of arthritis. Similarly, it rapidly reversed clinical disease progression in collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis and completely corrected CAIA-induced increase in monocyte Fcγ receptor II/III expression. Ter119 dose-dependently induced plasma chemokines CCL2, CCL5, CXCL9, CXCL10, and CCL11 with corresponding alterations in monocyte percentages in the blood and liver within 24 hours. Ter119 attenuated chemokine production from the synovial fluid and prevented the accumulation of inflammatory cells and complement components in the synovium. Ter119 could also accelerate the resolution of hypothermia and pulmonary edema in an acute lung injury model. We conclude that this inflammatory anti-erythrocyte antibody simultaneously triggers a highly efficient anti-inflammatory effect with broad therapeutic potential.
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| 2. |
- Jongerius, Ilse, et al.
(författare)
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The Role of Complement in Transfusion-Related Acute Lung Injury
- 2019
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Ingår i: Transfusion Medicine Reviews. - : Elsevier BV. - 0887-7963. ; 33:4, s. 236-242
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Forskningsöversikt (refereegranskat)abstract
- Transfusion-related acute lung injury (TRALI) is a life-threatening complication of acute respiratory distress occurring within 6 hours of blood transfusion. TRALI is one of the leading causes of transfusion-related fatalities and specific therapies are unavailable. Neutrophils are recognized as the major pathogenic cells, whereas T regulatory cells and dendritic cells appear to be important for protection against TRALI. The pathogenesis, however, is complex and incompletely understood. It is frequently postulated that the complement system plays an important role in the TRALI pathogenesis. In this article, we assess the evidence regarding the involvement of complement in TRALI from both human and animal studies. We hypothesize about the potential connection between the complement system and neutrophils in TRALI. Additionally, we draw parallels between TRALI and other acute pulmonary disorders of acute lung injury and acute respiratory distress syndrome regarding the involvement of complement. We conclude that, even though a role for complement in the TRALI pathogenesis seems plausible, studies investigating the role of complement in TRALI are remarkably limited in number and also present conflicting findings. Different types of TRALI animal models, diverse experimental conditions, and the composition of the gastrointestinal microbiota may perhaps all be factors which contribute to these discrepancies. More systematic studies are warranted to shed light on the contribution of the complement cascade in TRALI. The underlying clinical condition of the patient, which influences the susceptibility to TRALI, as well as the transfusion factor (antibody-mediated vs non–antibody-mediated), will be important to take into consideration when researching the contribution of complement. This should significantly increase our understanding of the role of complement in TRALI and may potentially result in promising new treatment strategies.
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| 3. |
- Kapur, Rick, et al.
(författare)
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Osteopontin mediates murine transfusion-related acute lung injury through stimulation of pulmonary neutrophil accumulation.
- 2019
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 134:1, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within 6 hours of a blood transfusion. There are no specific therapies available and the pathogenesis remains unclear. Pre-existing inflammation is a risk factor for TRALI and neutrophils (PMNs) are considered to be the major pathogenic cells mediating lung damage. Osteopontin (OPN) is a multifunctional protein expressed at sites of inflammation and, for example, is involved in pulmonary disorders, can regulate cellular migration and can function as a PMN-chemoattractant. We investigated whether OPN is involved in TRALI-induction by promoting PMN-recruitment to the lungs. Using a previously established murine TRALI model, we found that in contrast to wildtype (WT) mice, OPN knock-out (KO) mice were resistant to antibody-mediated PMN-dependent TRALI induction. Administration of purified OPN to the OPN KO mice, however, restored the TRALI response and pulmonary PMN-accumulation. Alternatively, blockade of OPN in WT mice using an anti-OPN antibody prevented the onset of TRALI induction. Using pulmonary immunohistochemistry, OPN could be specifically detected in the lungs of mice that suffered from TRALI. The OPN-mediated TRALI responses were independent from other PMN-chemoattractants including macrophage inflammatory protein (MIP)-2. These data indicate that OPN is critically required for induction of antibody-mediated murine TRALI through localization to the lungs and stimulation of pulmonary PMN-recruitment. This suggests that anti-OPN antibody-therapy may be a potential strategy to explore in targeting TRALI in patients.
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| 4. |
- McVey, Mark J, et al.
(författare)
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Transfusion-related Acute Lung Injury in the Perioperative Patient
- 2019
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Ingår i: Anesthesiology. - 1528-1175. ; 131:3, s. 693-715
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Forskningsöversikt (refereegranskat)abstract
- Transfusion-related acute lung injury is a leading cause of death associated with the use of blood products. Transfusion-related acute lung injury is a diagnosis of exclusion which can be difficult to identify during surgery amid the various physiologic and pathophysiologic changes associated with the perioperative period. As anesthesiologists supervise delivery of a large portion of inpatient prescribed blood products, and since the incidence of transfusion-related acute lung injury in the perioperative patient is higher than in nonsurgical patients, anesthesiologists need to consider transfusion-related acute lung injury in the perioperative setting, identify at-risk patients, recognize early signs of transfusion-related acute lung injury, and have established strategies for its prevention and treatment.
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| 5. |
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| 6. |
- Semple, John W, et al.
(författare)
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Transfusion-associated circulatory overload and transfusion-related acute lung injury.
- 2019
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 133:17, s. 1840-1853
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Forskningsöversikt (refereegranskat)abstract
- Transfusion-associated circulatory overload (TACO) and Transfusion-related acute lung injury (TRALI) are syndromes of acute respiratory distress which occur within 6 hours of blood transfusion. TACO and TRALI are the leading causes of transfusion-related fatalities and specific therapies are unavailable. Diagnostically, it remains very challenging to distinguish TACO and TRALI from underlying causes of lung injury and/or fluid overload as well as from each other. TACO is characterized by pulmonary hydrostatic (cardiogenic) edema, while TRALI presents as pulmonary permeability edema (noncardiogenic). The pathophysiology of both syndromes is complex and incompletely understood. A 2-hit model is generally assumed to underlie TACO and TRALI disease pathology where the first hit represents the clinical condition of the patient and the second hit is conveyed by the transfusion product. In TACO, cardiac- or renal impairment and positive fluid balance appear first hits while suboptimal fluid management or other components in the transfused product may enable the second hit. Remarkably, other factors beyond volume play a role in TACO. In TRALI, the first hit can, for example, be represented by inflammation while the second hit is assumed to be caused by anti-leukocyte antibodies or biological response modifiers (e.g. lipids). In this review, we provide an up-to-date overview of TACO and TRALI regarding clinical definitions, diagnostic strategies, pathophysiological mechanisms and potential therapies. More research is required to better understand the TACO and TRALI pathophysiology and more biomarker studies are warranted. Collectively, this may result in improved diagnostics and development of therapeutic approaches for these life-threating transfusion reactions.
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