Antibodies to major histocompatibility complex class II antigens directly prime neutrophils and cause acute lung injury in a two-event in vivo rat model.
Transfusion-related acute lung injury (TRALI) is a significant cause of mortality, especially after transfusions containing antibodies to major histocompatibility complex (MHC) class II antigens. We hypothesize that a first event induces both 1) polymorphonuclear neutrophils (PMNs) to express MHC class II antigens, and 2) activation of the pulmonary endothelium, leading to PMN sequestration, so that the infusion of specific MHC class II antibodies to these antigens causes PMN-mediated acute lung injury (ALI).



Rats were treated with saline (NS), endotoxin (lipopolysaccharide [LPS]), or cytokines (interferon-γ [IFNγ], macrophage colony-stimulating factor [MCSF], tumor necrosis factor-α [TNFα]); the PMNs were isolated; and the surface expression of the MHC class II antigen OX6 and priming by OX6 antibodies were measured by flow cytometry or priming assays.



A two-event model of ALI was completed with NS, LPS, or IFNγ/MCSF/TNFα (first events) and the infusion of OX6 (second event). Compared with NS incubation, rats treated with either LPS or IFNγ/MCSF/TNFα exhibited OX6 PMN surface expression, OX6 antibodies primed the formyl-methionyl-leucyl phenylalanine (fMLF)-activated respiratory burst, and PMN sequestration was increased. OX6 antibody infusion into LPS-incubated or IFNγ/MCSF/TNFα-incubated rats elicited ALI, the OX6 antibody was present on the PMNs, and PMN depletion abrogated ALI.



Proinflammatory first events induce PMN MHC class II surface expression, activation of the pulmonary endothelium, and PMN sequestration such that the infusion of cognate antibodies precipitates TRALI.
Research Laboratory, Bonfils Blood Center, Denver, Colorado.|Department of Surgery, University of Colorado Denver, Aurora, Colorado.
Marguerite R
MR
Kelher
Department of Surgery, University of Colorado Denver, Aurora, Colorado.
Anirban
A
Banerjee
Department of Surgery, University of Colorado Denver, Aurora, Colorado.
Fabia
F
Gamboni
Department of Surgery, University of Colorado Denver, Aurora, Colorado.
Cameron
C
Anderson
Research Laboratory, Bonfils Blood Center, Denver, Colorado.|Department of Surgery, University of Colorado Denver, Aurora, Colorado.|Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, Colorado.
Christopher C
CC
Silliman
D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D004727:Endothelium / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D016897:Respiratory Burst / Q000276:immunology; D065227:Transfusion Reaction
D000906:Antibodies; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides
Transfus Med. 2007 Apr;17(2):129-34
17430469
Blood. 2011 Jan 13;117(2):669-77
21030555
J Leukoc Biol. 2003 Apr;73(4):511-24
12660226
Kidney Int. 2001 Dec;60(6):2247-62
11737598
Clin Hemorheol Microcirc. 2014;56(2):175-85
23619201
J Clin Apher. 2009;24(3):122-9
19365816
Transfusion. 2002 Aug;42(8):1102
12385425
Vox Sang. 2007 Jul;93(1):78-82
17547569
Am J Physiol Lung Cell Mol Physiol. 2002 Aug;283(2):L460-7
12114209
Lung. 1995;173(2):127-37
7715254
Blood. 2014 May 29;123(22):3488-95
24747436
Blood. 2011 Jan 13;117(2):378-9
21233322
Transfusion. 2003 Apr;43(4):545-6
12662291
Transfusion. 2011 Dec;51(12):2549-54
21615744
Immunology. 2000 Dec;101(4):521-30
11122456
Inflammation. 2002 Aug;26(4):143-52
12184627
Immunology. 1993 May;79(1):119-24
8099565
Blood. 1997 Jun 1;89(11):4128-35
9166855
J Immunol. 2004 Aug 1;173(3):1994-2002
15265934
Transfusion. 2013 Jul;53(7):1442-9
23113676
J Exp Med. 1994 Jan 1;179(1):203-12
8270865
Transfus Med. 2004 Jun;14(3):225-30
15180814
Clin Exp Immunol. 2003 Sep;133(3):476-84
12930377
Transfusion. 2009 Mar;49(3):440-52
18980623
Haematologica. 1998 Jun;83(6):573-5
9676035
Vox Sang. 2010 Jan;98(1):70-7
19671122
Allergol Immunopathol (Madr). 2012 Mar-Apr;40(2):81-7
21652138
Blood. 2000 Dec 1;96(12):3958-63
11090084
Transfus Med. 2003 Jun;13(3):141-7
12791081
Hum Immunol. 1995 May;43(1):45-50
7558928
Blood Purif. 2010;29(4):321-6
20185904
Transplantation. 1997 Oct 27;64(8):1175-80
9355836
Crit Care Med. 2013 Mar;41(3):820-32
23348516
Blood. 2013 Mar 7;121(10):1690-700
23305733
J Am Soc Nephrol. 2011 Jun;22(6):1161-7
21617122
Transfusion. 2003 May;43(5):633-40
12702186
J Exp Med. 1998 Apr 6;187(7):1019-28
9529318
Transfusion. 2010 Aug;50(8):1732-42
20456698
Transfus Med Rev. 2009 Oct;23(4):266-83
19765516
Transfusion. 2003 Feb;43(2):185-91
12559014
Transfusion. 1985 Nov-Dec;25(6):573-7
4071603
Transfus Med Rev. 2004 Jul;18(3):184-8
15248168
J Immunol. 2014 Oct 1;193(7):3704-3716
25165152
J Heart Lung Transplant. 2002 Aug;21(8):882-9
12163088
Blood. 1995 Sep 15;86(6):2452-3
7545027
J Neurosci Res. 1988;20(2):147-57
3172275
J Immunol. 1993 Aug 1;151(3):1482-90
8335942
Immunology. 2006 Dec;119(4):562-71
17034427
J Leukoc Biol. 2001 Jul;70(1):80-6
11435489
Eur J Haematol. 2004 Oct;73(4):295-9
15347317
Blood. 2006 Oct 1;108(7):2455-62
16772606
Blood. 2009 Feb 26;113(9):2079-87
19131548
Am J Physiol Cell Physiol. 2002 Dec;283(6):C1592-603
12388071
J Immunol. 2003 Sep 1;171(5):2660-70
12928420
Transfusion. 2001 Oct;41(10):1244-8
11606823
Transplantation. 1990 Jun;49(6):1158-63
2113727
Immunol Lett. 2008 Jun 15;118(1):49-54
18400308
Vox Sang. 2011 Jan;100(1):122-8
21175662
Immunology. 2005 Mar;114(3):354-68
15720437
Kidney Int. 1999 May;55(5):1811-8
10231443
Anesth Analg. 2009 Mar;108(3):759-69
19224780
J Clin Invest. 1998 Apr 1;101(7):1458-67
9525989
Blood. 2007 Oct 15;110(8):2965-73
17562875