Advanced

Peripheral blood monocyte-derived chemokine blockade prevents murine transfusion-related acute lung injury (TRALI)

McKenzie, Christopher G J; Kim, Michael; Singh, Tarandeep K; Milev, Youli; Freedman, John and Semple, John W LU (2014) In Blood 123(22). p.503-3496
Abstract

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine antibody-mediated TRALI model was used to elucidate the roles of the F(ab')2 and Fc regions of a TRALI-inducing immunoglobulin G anti-major histocompatibility complex (MHC) class I antibody (34.1.2s). Compared with intact antibody, F(ab')2 fragments significantly increased serum levels of the neutrophil chemoattractant macrophage inflammatory... (More)

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine antibody-mediated TRALI model was used to elucidate the roles of the F(ab')2 and Fc regions of a TRALI-inducing immunoglobulin G anti-major histocompatibility complex (MHC) class I antibody (34.1.2s). Compared with intact antibody, F(ab')2 fragments significantly increased serum levels of the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2); however, pulmonary neutrophil levels were only moderately increased, and no pulmonary edema or mortality occurred. Fc fragments did not modulate any of these parameters. TRALI induction by intact antibody was completely abrogated by in vivo peripheral blood monocyte depletion by gadolinium chloride (GdCl3) or chemokine blockade with a MIP-2 receptor antagonist but was restored upon repletion with purified monocytes. The results suggest a two-step process for antibody-mediated TRALI induction: the first step involves antibody binding its cognate antigen on blood monocytes, which generates MIP-2 chemokine production that is correlated with pulmonary neutrophil recruitment; the second step occurs when antibody-coated monocytes increase Fc-dependent lung damage.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Acute Lung Injury, Animals, Blood Transfusion, Chemokine CXCL2, Chemokines, Disease Models, Animal, Gadolinium, Hypothermia, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, Male, Mice, Monocytes, Neutrophils, Spleen, Journal Article, Research Support, Non-U.S. Gov't
in
Blood
volume
123
issue
22
pages
8 pages
publisher
American Society of Hematology
external identifiers
  • scopus:84901711797
ISSN
1528-0020
DOI
10.1182/blood-2013-11-536755
language
English
LU publication?
no
id
e59fb551-7618-4752-9538-3901ce14e99c
date added to LUP
2016-09-23 12:00:49
date last changed
2017-10-22 05:19:37
@article{e59fb551-7618-4752-9538-3901ce14e99c,
  abstract     = {<p>Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine antibody-mediated TRALI model was used to elucidate the roles of the F(ab')2 and Fc regions of a TRALI-inducing immunoglobulin G anti-major histocompatibility complex (MHC) class I antibody (34.1.2s). Compared with intact antibody, F(ab')2 fragments significantly increased serum levels of the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2); however, pulmonary neutrophil levels were only moderately increased, and no pulmonary edema or mortality occurred. Fc fragments did not modulate any of these parameters. TRALI induction by intact antibody was completely abrogated by in vivo peripheral blood monocyte depletion by gadolinium chloride (GdCl3) or chemokine blockade with a MIP-2 receptor antagonist but was restored upon repletion with purified monocytes. The results suggest a two-step process for antibody-mediated TRALI induction: the first step involves antibody binding its cognate antigen on blood monocytes, which generates MIP-2 chemokine production that is correlated with pulmonary neutrophil recruitment; the second step occurs when antibody-coated monocytes increase Fc-dependent lung damage.</p>},
  author       = {McKenzie, Christopher G J and Kim, Michael and Singh, Tarandeep K and Milev, Youli and Freedman, John and Semple, John W},
  issn         = {1528-0020},
  keyword      = {Acute Lung Injury,Animals,Blood Transfusion,Chemokine CXCL2,Chemokines,Disease Models, Animal,Gadolinium,Hypothermia,Immunoglobulin Fab Fragments,Immunoglobulin Fc Fragments,Male,Mice,Monocytes,Neutrophils,Spleen,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  number       = {22},
  pages        = {503--3496},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Peripheral blood monocyte-derived chemokine blockade prevents murine transfusion-related acute lung injury (TRALI)},
  url          = {http://dx.doi.org/10.1182/blood-2013-11-536755},
  volume       = {123},
  year         = {2014},
}