scholarly journals Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury

2009 ◽  
Author(s):  
Mark R. Looney ◽  
John X. Nguyen ◽  
Yongmei Hu ◽  
Jessica A. Van Ziffle ◽  
Clifford A. Lowell ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Event Model ◽  
Platelet Depletion

Effects of platelet depletion on PMA-induced acute lung injury in awake sheep

1995 ◽  
Vol 101 (2) ◽  
pp. 207-217 ◽  
Author(s):  
Tsuyoshi Nakano ◽  
Kenji Miyamoto ◽  
Akira Aida ◽  
Shunichi Saito ◽  
Masaharu Nishimura ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Platelet Depletion

The Role of Recipient Platelets In the Prevention of Antibody-Mediated Transfusion Related Acute Lung Injury (TRALI)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3351-3351
Author(s):  
Yuhan Chen ◽  
Michael Kim ◽  
Arata Tabuchi ◽  
Wolfgang M. Kuebler ◽  
Rukhsana Aslam ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Conflicts Of Interest ◽  
Scid Mice ◽  
Lung Damage ◽  
Cell Mediated Immunity ◽  
Shock Lung ◽  
Inflammatory Milieu ◽  
Platelet Depletion

Abstract Abstract 3351 Transfusion related acute lung injury (TRALI) is a serious complication of transfusion. The pathogenesis of TRALI is not fully understood but previous findings have suggested that platelet depletion can protect mice in a two-hit model of TRALI (Looney et al J Clin Invest 119:3450, 2009). To further understand the role of platelets in preventing antibody-mediated TRALI, two mouse models of immune thrombocytopenia (ITP) were utilized. In the passive ITP model, SCID mice were injected with a monoclonal anti-platelet antibody (MWReg30) intraperitoneally (ip, 18 h before TRALI induction) or intravenously (iv, 2 h before TRALI induction). In the active ITP model, SCID mice were transferred with splenocytes from anti-CD61 immune GPIIIa-knockout mice and thrombocytopenia occurred within 2 weeks post transfer (Chow et al Blood 115;1247, 2010). TRALI induction was performed by injecting the various thrombocytopenic SCID mice with a murine monoclonal MHC class I antibody (mAb, 34-1 -2s) iv and several parameters were observed for up to 2 h post antibody injection. In control, non-thrombocytopenic SCID mice, 34-1 -2s injection caused severe systemic shock as noted by reduced rectal temperatures which was associated with significant lung damage and mortality (45%) within 1 hour of 34-1 -2s infusion as previously shown (Fung et al. Blood DOI 10.1182/blood-2010-05-284570). In contrast, while SCID mice depleted of platelets by the passive ip route had systemic shock, lung damage and a 60% mortality rate, those mice made thrombocytopenic by the iv route were completely protected from mortality. On the other hand, in the active ITP model, where the induced thrombocytopenia is associated with a proinflammatory anti-platelet immune response, no mortality was observed in those mice made thrombocytopenic by antibody-mediated immune mechanisms whereas 80% of mice rendered thrombocytopenic by CD8+ T cell-mediated immunity were dead within 1 hr post 34-1 -2s infusion. These results suggest that thrombocytopenia in itself does not protect against antibody-mediated TRALI severity but the nature of the thrombocytopenia induction (e.g. acute passive iv infusion or active ITP immune transfer) is important. In fact, depending on the inflammatory milieu associated with the thrombocytopenia, platelets may actually increase the severity of TRALI. Disclosures: No relevant conflicts of interest to declare.

The two-event model of transfusion-related acute lung injury

2006 ◽  
Vol 34 (Suppl) ◽  
pp. S124-S131 ◽  
Author(s):  
Christopher C. Silliman
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Event Model

PLASMA FRACTION FROM STORED PACKED RED BLOOD CELLS INDUCES ACUTE LUNG INJURY IN AN IN VIVORODENT TWO EVENT MODEL

Shock ◽  
2006 ◽  
Vol 25 (Supplement 1) ◽  
pp. 21
Author(s):  
T. Masuno ◽  
E. Moore ◽  
S. Damle ◽  
A. Cheng ◽  
M. Kelher ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Packed Red Blood Cells ◽  
Plasma Fraction ◽  
Event Model

Platelet depletion limits the severity but does not prevent the occurrence of experimental transfusion‐related acute lung injury

Transfusion ◽  
2020 ◽  
Vol 60 (4) ◽  
pp. 713-723 ◽  
Author(s):  
Fabrice Cognasse ◽  
Sofiane Tariket ◽  
Hind Hamzeh‐Cognasse ◽  
Charles‐Antoine Arthaud ◽  
Marie‐Ange Eyraud ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Platelet Depletion

The Two-Event Model of Transfusion-Related Acute Lung Injury: Antibodies to HNA-3a Cause PMN Cytotoxicity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 832-832 ◽  
Author(s):  
Brian R. Curtis ◽  
Marguerite R. Kelher ◽  
Nathan J.D. McLaughlin ◽  
Patricia M. Kopko ◽  
Christopher C. Silliman
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Sequestration ◽  
Endothelial Damage ◽  
Healthy Donors ◽  
Group Control ◽  
Event Model ◽  
Stored Blood

Abstract Transfusion related acute lung injury (TRALI) is a serious complication of blood administration. TRALI is neutrophil (PMN)-mediated and the pathogenesis is due to the infusion of antibodies directed against specific HLA (class I or II) or granulocyte antigens and may also be the result of two events: 1) a predisposing clinical condition of the patient resulting in PMN pulmonary sequestration followed by 2) the infusion of biologic response modifiers (BRMs), e.g. lipids from stored blood. These BRMs prime PMNs in vitro and cause PMN cytotoxicity in vivo resulting in endothelial damage, capillary leak and TRALI. We hypothesize that antibodies directed against specific PMN antigens cause rapid PMN priming and cytotoxicity in a two-event model, specific to the antigen they recognize. PMNs were isolated from healthy donors and 5b− (HNA-3a−) donors by standard techniques and were incubated for 3 min with 10% fresh plasma (FP) from healthy donors, plasma from three donors who had antibodies against HNA-3a and were implicated in TRALI, or 10% immune complexes (ICs) made from sera (+ control). Selected wells had Fab′2 fragments against the Fc receptors (CD16, CD32 & CD64). The maximal rate of O2− production was measured as cytochrome c reduction at 550 nm. Priming is defined as augmentation of the fMLP-activated respiratory burst (Table 1). We used an in vitro model of TRALI (Wyman AJP Cell 283: C1592, 2002) in which Human plumonary microvascular endothelial cells (HMVECs) were grown to 90% confluence and incubated with buffer or endotoxin (LPS) [200 ng/ml] for 6 hours. HNA-3a+ PMNs were added ± Fab′2 fragments, allowed to settle, and incubated for 30 min with FP or HNA-3a+ plasma. The plates were forcibly decanted and the viable HMVECs per mm2 were counted (Table 2). HNA-3a+ plasma significantly primed the PMN oxidase as compared to FP-treated controls (Table 1). Pre-treatment of PMNs with Fab′2 inhibited IC priming but did not affect other groups, and HNA-3a+ plasma did not prime HNA-3a− PMNs (data not shown). HNA-3a+ plasma ± LPS without PMNs did not affect HMVEC viability (data not shown), and HMVECs activated with LPS caused widespread PMN adherence. HNA-3a+ plasma plus HNA-3a+ PMNs caused destruction of LPS-activated HMVECs that was partially inhibited by Fab′2 fragments (Table 2). We conclude that HNA-3a+ plasma rapidly, effectively, and specifically primes HNA3+ PMNs. HNA-3a+ plasma can also serve as the second event in a two-event model of PMN-mediated HMVEC damage. Thus, antibodies directed against specific granulocyte antigens and lipids from stored blood may cause TRALI through a common final pathway of PMN activation. HNA-3a+ (5b+) plasma priming of HNA-3a+ PMNs Pre-tx/Group Control ICs FFP Donor 1 Donor 2 Donor 3 Units=nmol O2−/min; †=P<0.05 versus FFP controls; *=p<0.05 versus ICs. Buffer 2.7±0.5 8.8±0.7† 2.5±0.4 5.7±1.8† 6.5±† 5.0±1.0† Fab′2 2.1±0.8 3.2±0.4* 3.6±0.9 3.8±0.7 4.6±1.5 4.0±1.0 HNA-3a+ (5b+) plasma causes PMN cytotoxicity Pre-tx/Group Control LPS/PMNs LPS/PMNs/FFP LPS/PMNs/5b plasma Units=viable HMVECs/mm2; †=p<0.05 versus Controls and LPS/PMNs/FFP; *=p<0.05 versus LPS/PMN/5b+ plasma. Buffer 245±1 234±8 229±9 151±7† Fab′2 no data no data 240±9 190±*

SECRETARY PLA2 BLOCKADE PREVENTS ACUTE LUNG INJURY IN A TWO EVENT MODEL.

Shock ◽  
2004 ◽  
Vol 21 ◽  
pp. 68
Author(s):  
T. Masuno ◽  
E. Moore ◽  
E. Sarin ◽  
A. Cheng ◽  
C. Silliman
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Event Model
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