Nagano H, Nadeau K C, Takada M, Kusaka M, Tilney N L
Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Transplantation. 1997 Apr 27;63(8):1101-8. doi: 10.1097/00007890-199704270-00009.
The initial (0-24 hr), early (3-5 days), and late (7-14 days) events occurring in LBNF1 renal allografts transplanted into Lew recipients were examined to define precisely the sequential cellular and molecular kinetics during acute rejection. Grafts and spleens were harvested at 3, 6, 12, and 24 hr, and at 3, 5, 7, and 14 days and processed for morphology, immunohistology, and reverse transcriptase-polymerase chain reaction. Various factors (mRNA) were up-regulated sequentially in the allografts over time. In the initial phase, E-selectin and complement (C1 and C3) expression was noted within 6 hr, peaking by 24 hr. RANTES (regulated upon activation, normal T cell expressed and secreted) increased within 6 hr, and then again between 3 and 6 days. By immunohistology, MHC class II was up-regulated consistently after day 1. Intercellular adhesion molecule-1 expression increased after day 3; lymphocyte function-associated antigen-1+ infiltrating leukocytes peaked at day 5. Infiltrating CD8+ T lymphocytes increased strikingly between days 1 and 3, peaking at day 5; CD4+ cells infiltrated more slowly until day 5. The kinetics of ED1+ macrophages were similar to those of lymphocyte function-associated antigen-1+ cells. The CD4+ T cell-derived product, interleukin (IL)-2, peaked at 7 days. Interferon-gamma increased progressively up to 14 days. By 3 days, the macrophage-associated factor, transforming growth factor-beta, peaked; this was followed by increased IL-6 expression by day 5. IL-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase increased slowly until day 7, declining thereafter. Endothelin increased progressively over the 14-day follow-up period. Cytokine dynamics occurring in host spleen were similar to those noted in the allografts. Although acute rejection is primarily T cell mediated, adhesion molecules, macrophages, and their associated products may influence initial and later changes. The brisk expression of complement, E-selectin, and RANTES within the first few hours after engraftment may occur secondary to ischemic injury and trigger subsequent immunological events. Macrophages and their products may play a larger role in the process than hitherto appreciated.
对移植到Lewis受体体内的LBNF1同种异体肾移植中发生的初始（0 - 24小时）、早期（3 - 5天）和晚期（7 - 14天）事件进行了检查，以精确确定急性排斥反应期间细胞和分子的连续动力学变化。在3、6、12和24小时以及3、5、7和14天采集移植物和脾脏，并进行形态学、免疫组织学和逆转录聚合酶链反应处理。随着时间的推移，同种异体移植物中各种因子（mRNA）依次上调。在初始阶段，E - 选择素和补体（C1和C3）的表达在6小时内被检测到，24小时达到峰值。调节激活正常T细胞表达和分泌因子（RANTES）在6小时内增加，然后在3至6天再次增加。通过免疫组织学检测，MHC II类分子在第1天后持续上调。细胞间黏附分子 - 1的表达在第3天后增加；淋巴细胞功能相关抗原 - 1阳性浸润白细胞在第5天达到峰值。浸润的CD8 + T淋巴细胞在第1天至第3天显著增加，第5天达到峰值；CD4 +细胞浸润较慢，直到第5天。ED1 +巨噬细胞的动力学变化与淋巴细胞功能相关抗原 - 1阳性细胞相似。CD4 + T细胞衍生产物白细胞介素（IL） - 2在第7天达到峰值。干扰素 - γ在14天内逐渐增加。到第3天，巨噬细胞相关因子转化生长因子 - β达到峰值；随后在第5天白细胞介素 - 6表达增加。白细胞介素 - 1、肿瘤坏死因子 - α和诱导型一氧化氮合酶在第7天前缓慢增加，此后下降。内皮素在14天的随访期内逐渐增加。宿主脾脏中发生的细胞因子动态变化与同种异体移植物中观察到的相似。尽管急性排斥反应主要由T细胞介导，但黏附分子、巨噬细胞及其相关产物可能影响早期和后期的变化。移植后最初几小时内补体、E - 选择素和RANTES的快速表达可能继发于缺血性损伤并引发随后的免疫事件。巨噬细胞及其产物在这一过程中可能发挥比以往认识到的更大的作用。
