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

Abstract

BACKGROUND Transfusion‐related acute lung injury (TRALI) is a severe pulmonary reaction due to blood transfusions. The pathophysiology of this complication is still not widely elucidated by the scientific community, especially regarding the direct role of blood platelets within the cellular mechanism responsible for the development of TRALI. STUDY DESIGN AND METHODS In this study, a mouse model was used to induce the development of antibody‐mediated acute lung injury through injections of lipopolysaccharide and an anti–major histocompatibility complex Class I antibody. BALB/c mice were pretreated with an anti‐GPIbα antibody, which induces platelet depletion, or ML354, a protease receptor 4 pathway inhibitor, 30 minutes before TRALI induction. RESULTS Depletion of platelets before TRALI induction appeared to reduce the severity of TRALI without completely inhibiting its development. Also, inhibition of platelet activation by ML354 did not prevent the onset of TRALI. Finally, the stimuli used for TRALI induction also triggered specific platelet activation upon ex vivo stimulation. CONCLUSIONS This study suggests that blood platelets are not critically required for TRALI induction, although they are to some extent involved in its pathophysiology.

The contribution of recipient platelets in TRALI: has the jury reached a verdict?

“…In the April issue of TRANSFUSION, Cognasse and colleagues also investigate the effect of PLT depletion using a 34‐1‐2S–mediated TRALI mouse model. At 30 minutes before TRALI induction with 34‐1‐2S, they treated mice with an anti‐GPIbα to deplete PLTs.…”

“…The discrepancies between the previously mentioned studies may be explained by the different experimental methods to deplete PLTs, by different duration of depletion methods, or by using different experimental read‐outs for lung injury, despite the fact that in all of these studies, the mice were infused with 34‐1‐2S to induce TRALI. Additionally, when investigating the involvement of PLTs in murine TRALI, Strait and colleagues did not treat the mice with low‐dose LPS before induction of TRALI, in contrast to the other studies . Perhaps superimposed on these discrepancies is the observation that the gut microbiome is a critical factor as to whether 34‐1‐2S–mediated TRALI can initiate .…”

Evaluation of Platelet Responses in Transfusion-Related Acute Lung Injury (TRALI)

“…This is especially true for the clinically-relevant TRALI model based on injection of the anti-major histocompatibility complex (MHC) class I antibody, 34–1-2S [ 1 , 27 ]. Like in humans, this model features the 2 hits of TRALI pathophysiology with the first hit being represented by, for example, low levels of IL-10 (IL-10 KO mice or via depletion of CD4+ Tregs or DCs) [ 7 ], infusion of C-reactive protein (CRP) [ 28 ] or by priming with low-dose LPS [ 9 , [29] , [30] , [31] , [32] ]. The second hit is conveyed by the 34–1-2S antibody infusion.…”

“…Strikingly, several discrepancies have arisen regarding the role of recipient platelets in affecting TRALI responses by 34–1-2S [ 11 ]. Some studies have found recipient platelets to be pathogenic [ 29 , 37 ], while other studies found recipient platelets to be dispensable for the onset of TRALI [ 38 , 39 ] or not completely dispensable but with limited pathogenic involvement [ 30 , 31 ]. An early study by Looney et al found that in LPS-primed mice, in vivo platelet depletion using a rabbit anti-mouse platelet serum administered 2 hours before TRALI induction with 34–1-2 s protected against TRALI [ 29 ].…”

“…It cannot be excluded that the use of different read-outs, at least to some extent, could significantly affect the assessment and conclusion of the occurrence of significant lung injury. A recent study by Cognasse et al also examined the involvement of recipient platelets in 34–1-2S-mediated TRALI [ 31 ]. This study depleted platelets in vivo using a rat anti-GPIbα polyclonal Ab or they inhibited platelet activation by pre-treating mice with the PAR4-pathway inhibitor ML354 [ 31 ].…”