Asano Hiroshi, Lee Chih-Yuan, Fox-Talbot Karen, Koh Cheryl M, Erdinc Melek M, Marschner Susanne, Keil Shawn, Goodrich Raymond P, Baldwin William M
Department of Pathology, John Hopkins Medical Institutions, Baltimore, MD 21205-2196, USA.
Transplantation. 2007 Nov 15;84(9):1174-82. doi: 10.1097/01.tp.0000287318.94088.d7.
Functional leukocytes in blood transfusions can cause alloimmunization. Previous studies have shown that exposure of platelet concentrates to riboflavin and light (Mirasol PRT treatment) causes irreparable modification of nucleic acids. This treatment does not interfere with platelet function but does inhibit a wide range of immunological functions of leukocytes present in platelet concentrates. The current study evaluated the ability of Mirasol treatment to prevent alloimmunization by platelet transfusions in rats.
Lewis rats received eight transfusions of untreated or Mirasol-treated platelets containing leukocytes from DA rats. Animals were subsequently challenged with a heart transplant under cyclosporine treatment.
Mirasol treatment caused apoptosis of the leukocytes as measured by annexin V and CD45 staining. Complement split products were deposited on the apoptotic bodies in the platelet pack. The primary and secondary immunoglobulin (Ig) M and IgG responses in rats that received Mirasol-treated platelets were almost completely abolished compared to animals that received untreated platelets. Untreated platelet transfusions elicited strong IgG responses that were associated with rapid rejection of subsequent heart transplants. Rejected hearts contained macrophage infiltrates and C4d deposits. In contrast, no grafts were rejected by recipients transfused with Mirasol-treated platelets. Macrophage infiltrates and C4d deposits were decreased in these grafts. Recipients that were presensitized to untreated platelets were capable of producing a memory response to Mirasol-treated platelets that caused accelerated rejection of subsequent transplants.
Transfusions of platelets that were treated with riboflavin and ultraviolet light prevented presensitization to transplants. However, Mirasol-treated platelets were immunogenic in presensitized recipients.
输血中的功能性白细胞可导致同种免疫。先前的研究表明，将血小板浓缩物暴露于核黄素和光下（Mirasol PRT处理）会导致核酸发生不可修复的修饰。这种处理不会干扰血小板功能，但会抑制血小板浓缩物中存在的白细胞的多种免疫功能。本研究评估了Mirasol处理预防大鼠血小板输血引起的同种免疫的能力。
Lewis大鼠接受8次输注来自DA大鼠的未处理或经Mirasol处理的含白细胞的血小板。随后在环孢素治疗下对动物进行心脏移植挑战。
通过膜联蛋白V和CD45染色测量，Mirasol处理导致白细胞凋亡。补体裂解产物沉积在血小板包中的凋亡小体上。与接受未处理血小板的动物相比，接受Mirasol处理血小板的大鼠的初次和二次免疫球蛋白（Ig）M和IgG反应几乎完全被消除。未处理的血小板输血引发强烈的IgG反应，这与随后心脏移植的快速排斥相关。被排斥的心脏含有巨噬细胞浸润和C4d沉积。相比之下，接受Mirasol处理血小板输血的受体没有排斥任何移植物。这些移植物中的巨噬细胞浸润和C4d沉积减少。对未处理血小板预先致敏的受体能够对Mirasol处理的血小板产生记忆反应，从而导致随后移植的加速排斥。
用核黄素和紫外线处理的血小板输血可预防对移植的预先致敏。然而，Mirasol处理的血小板在预先致敏的受体中具有免疫原性。
