Brandt M, Derner G, Boeke K, Phillips M L, Steinhoff G, Haverich A
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.
Eur J Cardiothorac Surg. 1997 Nov;12(5):781-6. doi: 10.1016/s1010-7940(97)00251-0.
Adhesion molecules regulate the infiltration of leukocytes into the graft during rejection after lung transplantation. The first step of the adhesion cascade is mediated by selectins. Sialyl-LewisX is a ligand of P-selectin. The purpose of the study was to evaluate SLX, a synthetic oligosaccharide analog of Sialyl-LewisX, for anti-rejection prophylaxis after allogeneic and xenogeneic left lateral, orthotopic rat lung transplantation.
In groups A and B, allogeneic lung transplantation was performed using fully incompatible rat strains (donors: Dark-Agouti (RT1a); recipients: Lewis (RT11)). In group A (n = 10), recipients recieved 200 microg/d SLX i.v. on day 0-4. Group B rats (n = 10) served as untreated controls. The animals were sacrificed on days 5 and 10, respectively. In groups C and D, xenogenic lung transplantation was performed using Gold Syrian hamsters as donors and Lewis rats as recipients. In group C (n = 10), recipients received 200 microg/d SLX i.v. on day 0-4. Group D rats (n = 10) served as untreated controls. The animals were sacrificed on days 2 and 5, respectively. Rejection was graded by histology from 0 (no rejection) to 5 (necrosis). By immunhistology, alveolar, interstitial CD11a, CD18 and VLA-4 positive leukocytes were counted.
Histologically, there were a lower grade of rejection (A: 2.7 +/- 0.6; B: 4.0 +/- 0.0; P < 0.05) and fewer CD11a positive leukocytes (A: 66 +/- 27; B: 186 +/- 73; P < 0.05) on day 5 in the SLX-treated allograft group compared to the untreated group. In xenotransplantation, SLX also reduced the grade of rejection (C: 3.3 +/- 0.5; D: 4.7 +/- 0.5; P < 0.05) and the number of CD11a positive leukocytes (C: 145 +/- 22; D: 176 +/- 20; P < 0.05) on day 2.
It is concluded, that the administration of SLX significantly reduces allograft rejection. After discontinuation treatment with SLX unmodified rejection appeared. SLX also modifies xenograft rejection, but to a lesser extent, and xenograft necrosis appeared during treatment in this model.
黏附分子在肺移植排斥反应过程中调节白细胞向移植物内浸润。黏附级联反应的第一步由选择素介导。唾液酸化路易斯X是P选择素的配体。本研究旨在评估唾液酸化路易斯X的合成寡糖类似物SLX对大鼠同种异体和异种原位左肺移植术后抗排斥反应的预防作用。
A组和B组采用完全不相容的大鼠品系进行同种异体肺移植（供体：黑褐大鼠（RT1a）；受体：刘易斯大鼠（RT11））。A组（n = 10）受体于第0至4天静脉注射200μg/d SLX。B组大鼠（n = 10）作为未治疗对照。分别于第5天和第10天处死动物。C组和D组采用金黄叙利亚仓鼠作为供体、刘易斯大鼠作为受体进行异种肺移植。C组（n = 10）受体于第0至4天静脉注射200μg/d SLX。D组大鼠（n = 10）作为未治疗对照。分别于第2天和第5天处死动物。通过组织学将排斥反应从0级（无排斥反应）至5级（坏死）进行分级。通过免疫组织学方法对肺泡、间质中CD11a、CD18和VLA - 4阳性白细胞进行计数。
组织学检查显示，与未治疗组相比，SLX治疗的同种异体移植组在第5天时排斥反应分级较低（A组：2.7±0.6；B组：4.0±0.0；P < 0.05），CD11a阳性白细胞数量较少（A组：66±27；B组：186±73；P < 0.05）。在异种移植中，SLX也降低了第2天时的排斥反应分级（C组：3.3±0.5；D组：4.7±0.5；P < 0.05）以及CD11a阳性白细胞数量（C组：145±22；D组：176±20；P < 0.05）。
得出结论，SLX的给药显著降低了同种异体移植排斥反应。停用SLX治疗后出现未改变的排斥反应。SLX也改善了异种移植排斥反应，但程度较小，且在该模型的治疗过程中出现了异种移植坏死。
