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C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury

Kapur, Rick; Kim, Michael; Shanmugabhavananthan, Shanjeevan; Liu, Jonathan; Li, Yuan LU and Semple, John W LU (2015) In Blood 126(25). p.51-2747
Abstract

Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress triggered by blood transfusions and is the leading cause of transfusion-related mortality. TRALI has primarily been attributed to passive infusion of HLA and/or human neutrophil antigen antibodies present in transfused blood products, and predisposing factors such as inflammation are known to be important for TRALI initiation. Because the acute-phase protein C-reactive protein (CRP) is highly upregulated during infections and inflammation and can also enhance antibody-mediated responses such as in vitro phagocytosis, respiratory burst, and in vivo thrombocytopenia, we investigated whether CRP affects murine antibody-mediated TRALI induced by the... (More)

Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress triggered by blood transfusions and is the leading cause of transfusion-related mortality. TRALI has primarily been attributed to passive infusion of HLA and/or human neutrophil antigen antibodies present in transfused blood products, and predisposing factors such as inflammation are known to be important for TRALI initiation. Because the acute-phase protein C-reactive protein (CRP) is highly upregulated during infections and inflammation and can also enhance antibody-mediated responses such as in vitro phagocytosis, respiratory burst, and in vivo thrombocytopenia, we investigated whether CRP affects murine antibody-mediated TRALI induced by the anti-major histocompatibility complex antibody 34-1-2s. We found that BALB/c mice injected with 34-1-2s or CRP alone were resistant to TRALI, however mice injected with 34-1-2s together with CRP had significantly enhanced lung damage and pulmonary edema. Mechanistically, 34-1-2s injection with CRP resulted in a significant synergistic increase in plasma levels of the neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and pulmonary neutrophil accumulation. Importantly, murine MIP-2 is the functional homolog of human interleukin-8, a known risk factor for human TRALI. These results suggest that elevated in vivo CRP levels, like those observed during infections, may significantly predispose recipients to antibody-mediated TRALI reactions and support the notion that modulating CRP levels is an effective therapeutic strategy to reduce TRALI severity.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Acute Lung Injury, Animals, Autoantibodies, Blood Transfusion, C-Reactive Protein, Disease Models, Animal, Histocompatibility Antigens Class I, Male, Mice, Mice, Inbred BALB C, Journal Article, Research Support, Non-U.S. Gov't
in
Blood
volume
126
issue
25
pages
5 pages
publisher
American Society of Hematology
external identifiers
  • Scopus:84951269290
ISSN
1528-0020
DOI
10.1182/blood-2015-09-672592
language
English
LU publication?
no
id
f44ee314-e307-45f4-b3d7-33383451eff0
date added to LUP
2016-09-23 11:57:31
date last changed
2016-10-13 05:14:11
@misc{f44ee314-e307-45f4-b3d7-33383451eff0,
  abstract     = {<p>Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress triggered by blood transfusions and is the leading cause of transfusion-related mortality. TRALI has primarily been attributed to passive infusion of HLA and/or human neutrophil antigen antibodies present in transfused blood products, and predisposing factors such as inflammation are known to be important for TRALI initiation. Because the acute-phase protein C-reactive protein (CRP) is highly upregulated during infections and inflammation and can also enhance antibody-mediated responses such as in vitro phagocytosis, respiratory burst, and in vivo thrombocytopenia, we investigated whether CRP affects murine antibody-mediated TRALI induced by the anti-major histocompatibility complex antibody 34-1-2s. We found that BALB/c mice injected with 34-1-2s or CRP alone were resistant to TRALI, however mice injected with 34-1-2s together with CRP had significantly enhanced lung damage and pulmonary edema. Mechanistically, 34-1-2s injection with CRP resulted in a significant synergistic increase in plasma levels of the neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and pulmonary neutrophil accumulation. Importantly, murine MIP-2 is the functional homolog of human interleukin-8, a known risk factor for human TRALI. These results suggest that elevated in vivo CRP levels, like those observed during infections, may significantly predispose recipients to antibody-mediated TRALI reactions and support the notion that modulating CRP levels is an effective therapeutic strategy to reduce TRALI severity.</p>},
  author       = {Kapur, Rick and Kim, Michael and Shanmugabhavananthan, Shanjeevan and Liu, Jonathan and Li, Yuan and Semple, John W},
  issn         = {1528-0020},
  keyword      = {Acute Lung Injury,Animals,Autoantibodies,Blood Transfusion,C-Reactive Protein,Disease Models, Animal,Histocompatibility Antigens Class I,Male,Mice,Mice, Inbred BALB C,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {12},
  number       = {25},
  pages        = {51--2747},
  publisher    = {ARRAY(0x90251c8)},
  series       = {Blood},
  title        = {C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury},
  url          = {http://dx.doi.org/10.1182/blood-2015-09-672592},
  volume       = {126},
  year         = {2015},
}