Enhancement of endothelial permeability by coculture with peripheral blood mononuclear cells in the presence of HLA Class II antibody that was associated with transfusion-related acute lung injury.
BACKGROUND
HLA Class II antibody-initiated activation of monocytes possessing the corresponding antigen is thought to participate in the pathogenesis of transfusion-related acute lung injury (TRALI). Pulmonary edema, a hallmark of TRALI, is caused by increasing vascular permeability.


METHODS
To investigate the contribution of HLA Class II antibody and monocytes to the development of pulmonary edema in TRALI, we studied whether the permeability of human lung microvascular endothelial cells (HMVECs) could be enhanced by coculturing HMVECs with peripheral blood mononuclear cells (PBMNCs) in the presence of HLA Class II antibody-containing plasma, which was implicated in TRALI (anti-HLA-DR plasma). In addition, similar experiments were performed with human umbilical vein endothelial cells (HUVECs). The endothelial permeability to fluoresceinated dextran, which was added from the start of coculture, was measured.


RESULTS
The coculture of HMVECs or HUVECs with PBMNCs in the presence of anti-HLA-DR plasma resulted in the increase of endothelial permeability in the corresponding antigen-antibody-dependent manner. CV-3988, a platelet-activating factor (PAF) receptor antagonist, almost completely suppressed the increase in endothelial permeability. Neutralizing antibodies to tumor necrosis factor (TNF)-α alone and simultaneous addition of the antibodies to TNF-α and interleukin (IL)-1β to the coculture partially suppressed the permeability increase of HMVECs and HUVECs, respectively.


CONCLUSIONS
HLA Class II antibody and monocytes in the corresponding antigen-antibody combination caused the enhancement of endothelial permeability. PAF, TNF-α, and/or IL-1β might be involved in the endothelial permeability increase. HLA Class II antibody-initiated monocyte activation could lead to the development of pulmonary edema in TRALI.
Hokkaido Red Cross Blood Center, Sapporo, Japan.
Shinobu
S
Wakamoto
Mitsuhiro
M
Fujihara
Daisuke
D
Takahashi
Koichi
K
Niwa
Shinichiro
S
Sato
Toshiaki
T
Kato
Hiroshi
H
Azuma
Hisami
H
Ikeda
D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology*; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D011654:Pulmonary Edema / Q000209:etiology / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000276:immunology; D018077:Receptors, Leukotriene / Q000276:immunology; D065227:Transfusion Reaction; D014471:Umbilical Veins / Q000166:cytology
D057134:Antibodies, Neutralizing; D006684:HLA-DR Antigens; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; C039351:platelet activating factor receptor; C083169:leukotriene D4 receptor