C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury
(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.
(Less)
- author
- Kapur, Rick ; Kim, Michael ; Shanmugabhavananthan, Shanjeevan ; Liu, Jonathan ; Li, Yuan LU and Semple, John W LU
- organization
- publishing date
- 2015-12-17
- 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
- pmid:26453659
- 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
- 2024-06-28 15:39:42
@article{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}},
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}},
language = {{eng}},
month = {{12}},
number = {{25}},
pages = {{51--2747}},
publisher = {{American Society of Hematology}},
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}},
doi = {{10.1182/blood-2015-09-672592}},
volume = {{126}},
year = {{2015}},
}