PMID- 35914412
OWN - NLM
STAT- MEDLINE
DCOM- 20220920
LR  - 20221019
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 150
DP  - 2022 Oct
TI  - Polymorphonuclear neutrophil activation by Src phosphorylation contributes to 
      HLA-A2 antibody-induced transfusion-related acute lung injury.
PG  - 9-19
LID - S0161-5890(22)00199-7 [pii]
LID - 10.1016/j.molimm.2022.04.010 [doi]
AB  - Human leukocyte antigen (HLA)-A2 antibody contributes to the pathogenesis of 
      transfusion-related acute lung injury (TRALI) via polymorphonuclear neutrophil 
      (PMN) activation, but the signaling pathways involved this process remain largely 
      undefined. In this study, we sought to study the signaling pathways involved in 
      the pathogenesis of HLA-A2-induced TRALI. Lipopolysaccharide (LPS), and the 
      plasma from the HLA-A2 antibody-positive donors were utilized to establish a rat 
      model of TRALI. Human pulmonary endothelial cells (HPMECs) were in vitro 
      co-cultured with HLA-A2 antibody-treated PMNs and then treated with LPS to induce 
      a cytotoxicity model. The effects of HLA-A2 antibody on HPMEC injury were 
      evaluated in this model. Besides, dasatinib was used to block the Src 
      phosphorylation to explore whether Src involved in the TRALI or HPMEC injury 
      induced by HLA-A2 antibody. The HLA-A2 antibody plus LPS induced TRALI and 
      stimulated PMN activation in rats. HLA-A2 antibody-induced TRALI could be 
      attenuated via depletion of PMN. HLA-A2 antibody activated NF-kappaB and NLRP3 
      inflammasome. In addition, HLA-A2 antibody aggravated the HPMEC injuries and the 
      release of PMN surfaces makers, but dasatinib treatment reversed this effect, 
      indicating that HLA-A2 antibody activated PMNs and exacerbated TRALI by 
      stimulating phosphorylation of Src followed by activation of NF-kappaB and NLRP3 
      inflammasome, which was validated in vivo. In summary, HLA-A2 induced PMNs by 
      activating NF-kappaB/NLRP3 inflammasome via phosphorylated-Src elevation, thereby 
      exacerbating TRALI. This study highlights promising target for the treatment of 
      antibody-mediated TRALI.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Le, Aiping
AU  - Le A
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China. Electronic address: leaiping@126.com.
FAU - Liu, Wei
AU  - Liu W
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China.
FAU - Wu, Chenggao
AU  - Wu C
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China.
FAU - Hu, Piaoping
AU  - Hu P
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China.
FAU - Zou, Juan
AU  - Zou J
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China.
FAU - Wu, Yize
AU  - Wu Y
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China.
FAU - Kuang, Linju
AU  - Kuang L
AD  - Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang 
      University, Nanchang 330006, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220730
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Antibodies)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Animals
MH  - Antibodies
MH  - Dasatinib/metabolism/pharmacology
MH  - Endothelial Cells
MH  - HLA Antigens
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Lipopolysaccharides/metabolism/pharmacology
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Neutrophils
MH  - Phosphorylation
MH  - Rats
MH  - *Transfusion Reaction/metabolism
MH  - *Transfusion-Related Acute Lung Injury/metabolism
MH  - src-Family Kinases/*metabolism
OTO - NOTNLM
OT  - Human leukocyte antigen-A2
OT  - NF-kappaB
OT  - NLRP3
OT  - Polymorphonuclear neutrophils
OT  - Src
OT  - Transfusion-related acute lung injury
COIS- Conflicts of interest The authors declare no conflicts of interest.
EDAT- 2022/08/02 06:00
MHDA- 2022/09/21 06:00
CRDT- 2022/08/01 18:19
PHST- 2021/09/06 00:00 [received]
PHST- 2022/02/18 00:00 [revised]
PHST- 2022/04/21 00:00 [accepted]
PHST- 2022/08/02 06:00 [pubmed]
PHST- 2022/09/21 06:00 [medline]
PHST- 2022/08/01 18:19 [entrez]
AID - S0161-5890(22)00199-7 [pii]
AID - 10.1016/j.molimm.2022.04.010 [doi]
PST - ppublish
SO  - Mol Immunol. 2022 Oct;150:9-19. doi: 10.1016/j.molimm.2022.04.010. Epub 2022 Jul 
      30.