Background

Donor leukocytes are intrinsically involved in acute lung allograft rejection, via self-presentation of donor antigens to recipient leukocytes. Therapeutic modalities to remove donor leukocytes are currently unavailable. We evaluated if a vascular flush immediately following preservation can be used for this purpose.

Methods

A post-preservation flush was performed with STEEN solution in n = 6 porcine lungs following static cold storage. The first 500 ml effluent from the left atrium was collected and an inflammatory profile performed.

Results

A total of 1.17 billion (±2.8 × 10⁸) viable leukocytes were identified within the effluent. T cells were the dominant cell population, representing 82% of the total mobilised leukocytes, of which <0.01% were regulatory T cells. IL-18 was the most abundant cytokine, with a mean concentration of 84,216 pg (±153,552 pg). In addition, there was a mean concentration of 8819 ng (±4415) cell-free mitochondrial DNA.

Conclusion

There is an immediate transfer of donor leukocytes, cytokines and damage-associated molecular patterns following reperfusion. Such a pro-inflammatory donor load may enhance alloantigen presentation and drive recipient alloimmune responses. A post-preservation flush may therefore be an effective method for reducing the immune burden of the donor lung prior to transplantation.

中文翻译：

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保存后的血管冲洗可在肺移植之前去除大量供体白细胞

背景

通过将供体抗原自我呈递给受体白细胞，供体白细胞固有地参与了急性肺移植排斥反应。目前尚无用于去除供体白细胞的治疗方法。我们评估了保存后立即进行的血管冲洗是否可用于此目的。

方法

 静态冷藏后，在n = 6的猪肺中用STEEN溶液进行保存后冲洗。收集来自左心房的第一批500 ml流出物，并进行炎症分析。

结果

废水中共鉴定出11.7亿（±2.8×10 ⁸）个活白细胞。T细胞是占主导地位的细胞群，占总动员白细胞的82％，其中<0.01％是调节性T细胞。IL-18是最丰富的细胞因子，平均浓度为84,216 pg（±153,552 pg）。此外，平均浓度为8819 ng（±4415）无细胞线粒体DNA。

结论

再灌注后，供体白细胞，细胞因子和损伤相关分子模式立即转移。这样的促炎性供体负荷可以增强同种抗原呈递并驱动受体同种免疫反应。因此，保存后冲洗可能是减少移植前供体肺部免疫负担的有效方法。