Transfusion-Related Acute Lung Injury: The Work of DAMPs*

Abstract

Current notions in immunology hold that not only pathogen-mediated tissue injury but any injury activates the innate immune system. In principle, this evolutionarily highly conserved, rapid first-line defense system responds to pathogen-induced injury with the creation of infectious inflammation, and non-pathogen-induced tissue injury with ‘sterile’ tissue inflammation. In this review, evidence has been collected in support of the notion that the transfusion-related acute lung injury induces a ‘sterile’ inflammation in the lung of transfused patients in terms of an acute innate inflammatory disease. The inflammatory response is mediated by the patient’s innate immune cells including lung-passing neutrophils and pulmonary endothelial cells, which are equipped with pattern recognition receptors. These receptors are able to sense injury-induced, damage-associated molecular patterns (DAMPs) generated during collection, processing, and storage of blood/blood components. The recognition process leads to activation of these innate cells. A critical role for a protein complex known as the NLRP3 inflammasome has been suggested to be at the center of such a scenario. This complex undergoes an initial ‘priming’ step mediated by 1 class of DAMPs and then an ‘activating’ step mediated by another class of DAMPs to activate interleukin-1beta and interleukin-18. These 2 cytokines then promote, via transactivation, the formation of lung inflammation.

Nutlin-3-induced redistribution of chromatin-bound IFI16 in human hepatocellular carcinoma cells in vitro is associated with p53 activation

“…In the present study, we detected the increased expression level of IFNB1 mRNA in Nutlin-3-treated SMMC-7721 cells, which promotes the anti- [45] . The function of the injury-activated innate immune system is similar to the two sides of a coin [46] . According to the danger hypothesis [47] , over-expressed IFI16 protein released in the extracellular niche acts as a novel alarmin propagating the damaged-signal [32] .…”

Case study of transfusion related acute lung injury in intensive care unit

“…However, its etiology is based on the wellknown "two-hit" hypothesis which includes the clinical condition (pre-existing pathology -first hit) of the patient and the transfusion of blood products, especially plasma (second hit). [2,[11][12][13][14] The vast majority of cases mention that the pre-existence of HLA class I, class II and HNA antibodies in the plasma of the donor, react with the neutrophils of the already very sensitive pulmonary mucosa. In a very smaller percentage of cases, it is reported that the pre-existing heavy pathology of the patient could result in a systemic inflammation of lungs which leads to the accumulation of neutrophils in their microvasculature.…”

“…However, further research is required for the proof of this hypothesis. [2,12,13,15] In many cases TRALI is confused with other diseases. Therefore, possible causes of acute pulmonary oedema should be excluded, which may be acute haemolytic reaction, pneumonia and cardiogenic pulmonary oedema.…”

Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation

“…Indeed, we have found that the continuous oxygenation of the acellular perfusate by ventilation of the lung provides ample oxygen delivery to the ex vivo lung with preservation of function over 12 h of EVLP. This avoids the problem of a limited lifespan of red blood cells within the harsh perfusion environment and the resultant production of pro-inflammatory RBC breakdown products [13]. It also significantly simplifies clinical use.…”