TY - JOUR
T1 - A pulmonary endothelial amplification loop aggravates ex-vivo transfusion-related acute lung injury via increased toll-like receptor 4 and intra-cellular adhesion molecule-1 expression
AU - Morsing, Sofia K. H.
AU - Zeeuw van der Laan, Eveline
AU - van Stalborch, Annemarieke D.
AU - van Buul, Jaap D.
AU - Kapur, Rick
AU - Vlaar, Alexander P.
N1 - Funding Information: This work was supported by ZonMW NWO Vici grant #91819632 (JDvB). Prof Dr Alexander P. J Vlaaris supported by ZonMW NWO VIDI grant #09150172010047. Publisher Copyright: © 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.
PY - 2022/10
Y1 - 2022/10
N2 - Background: Transfusion-Related Acute Lung Injury (TRALI) is a life-threatening complication of blood transfusions characterized by pulmonary endothelial cell damage and edema, with a high incidence in critically ill patients. The pathophysiology of TRALI is unresolved, but can generally be hypothesized to follow a 2-hit model in which the first hit is elicited by the underlying clinical condition of the patient (e.g., inflammation, which can be reflected by LPS in experimental models), and the second hit is delivered by the blood transfusion product (e.g., HLA class I antibodies). Here, we report a synergistic role for LPS and HLA class I antibody binding to pulmonary endothelium resulting in enhanced inflammatory responses. Materials and Methods: Pulmonary endothelial cells were treated with PBS or low-dose LPS, exclusively or in combination with anti-HLA class I. Endothelial surface expression of HLA class I, TLR4, and inflammatory marker ICAM-1 were measured, and trans-endothelial migration (TEM) of neutrophils was investigated. Results: LPS treatment of pulmonary endothelium enhanced HLA class I antibody binding, and combined LPS and HLA class I antibody binding enhanced TLR4 (LPS receptor) and ICAM-1 expression on the endothelial cell surface. Low-dose LPS and HLA antibody together also increased neutrophil TEM under physiological flow by on average 5-fold. Conclusion: We conclude that LPS and anti-HLA class I antibody have the ability to activate the pulmonary endothelium into a spiral of increasing inflammation, opening the opportunity to potentially block TLR4 to prevent or reduce the severity of TRALI in vivo.
AB - Background: Transfusion-Related Acute Lung Injury (TRALI) is a life-threatening complication of blood transfusions characterized by pulmonary endothelial cell damage and edema, with a high incidence in critically ill patients. The pathophysiology of TRALI is unresolved, but can generally be hypothesized to follow a 2-hit model in which the first hit is elicited by the underlying clinical condition of the patient (e.g., inflammation, which can be reflected by LPS in experimental models), and the second hit is delivered by the blood transfusion product (e.g., HLA class I antibodies). Here, we report a synergistic role for LPS and HLA class I antibody binding to pulmonary endothelium resulting in enhanced inflammatory responses. Materials and Methods: Pulmonary endothelial cells were treated with PBS or low-dose LPS, exclusively or in combination with anti-HLA class I. Endothelial surface expression of HLA class I, TLR4, and inflammatory marker ICAM-1 were measured, and trans-endothelial migration (TEM) of neutrophils was investigated. Results: LPS treatment of pulmonary endothelium enhanced HLA class I antibody binding, and combined LPS and HLA class I antibody binding enhanced TLR4 (LPS receptor) and ICAM-1 expression on the endothelial cell surface. Low-dose LPS and HLA antibody together also increased neutrophil TEM under physiological flow by on average 5-fold. Conclusion: We conclude that LPS and anti-HLA class I antibody have the ability to activate the pulmonary endothelium into a spiral of increasing inflammation, opening the opportunity to potentially block TLR4 to prevent or reduce the severity of TRALI in vivo.
KW - HLA class I
KW - TEM
KW - TLR4
KW - TRALI
KW - pulmonary EC
UR - http://www.scopus.com/inward/record.url?scp=85136551238&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/trf.17076
DO - https://doi.org/10.1111/trf.17076
M3 - Article
C2 - 36004763
SN - 0041-1132
VL - 62
SP - 1961
EP - 1966
JO - Transfusion
JF - Transfusion
IS - 10
ER -