腺泡细胞凋亡在大鼠胰腺移植急性排斥反应中的意义

目的：观察移植胰腺的腺泡细胞凋亡及其与急性排斥反应的关系。方法：选用SD和Wistar大鼠进行全胰十二指移植。实验分为同基因移植组（Wistar→Wistar）和异基因移植组（SD→Wistar）两组。于术后第3d、5d和7d分批处死受体，取移植胰腺标本用HE染色和原位末端标记（TUNEL）技术检测移植胰腺切片，进行排斥反应的病理学评分和计数凋亡指数（AI）。结果：发生凋亡的细胞主要是腺泡细胞，同基因移植组胰腺有散在的腺泡细胞凋亡，AI在术后无明显变化。异基因移植组胰腺腺泡细胞凋亡在术后第3d、5d和7d逐渐升高，AI与急性排斥反应的病理学评分成正相关。结论：细胞凋亡与移植胰腺急性排斥反应的严重程度显著相关，凋亡指数可作为判断移植物损伤程度的指标，对急性排斥反应的诊断有一定的参考价值。     

细胞凋亡在大鼠胰腺移植急性排斥反应中的作用

目的探讨细胞凋亡和相关因子Fas、FasL、bcl-2和bax在大鼠胰腺移植急性排斥反应中的作用,评价十二指肠黏膜活检在胰腺移植中诊断排斥反应的价值。方法选SD和Wistar大鼠行全胰十二指肠移植,实验分同基因胰腺移植组和异基因胰腺移植组。于移植术后第3、5及7d分批处死受体,取移植胰腺和十二指肠标本用HE染色和原位末端脱氧核糖核苷酸转移酶标记技术(TUNEL)检测移植物。免疫组化法检测移植后胰腺和十二指肠Fas、FasL、bcl-2和bax的表达。结果异基因胰腺移植组胰腺和十二指肠病理评分相同者占61.1%(11/18);评分不同者占38.9%(7/18),其中胰腺评分较高者6例,十二指肠黏膜评分较高者仅1例。异基因胰腺移植组胰腺和十二指肠病理学评分和细胞凋亡指数均明显高于同基因胰腺移植组(P<0.05,P<0.01)。胰腺和十二指肠细胞凋亡指数与急性排斥反应的病理学评分成正相关(r=0.965,P<0.01;r=0.942,P<0.01)。随着术后时间延长,排斥反应分级上升,细胞凋亡增加,FasL表达升高,在异基因移植组bcl-2表达下降,而Fas和bax表达无明显变化。结论细胞凋亡与移植胰腺急性排斥反应的严重程度呈正相关,细胞凋亡指数可作为判断移植物损伤程度的指标。FasL和bcl-2与胰腺移植急性排斥及组织损伤密切相关。十二指肠黏膜活检有助于判断有无胰腺急性排斥反应发生。     

Fas配体表达对同种胰岛移植的影响

目的探究睾丸细胞FasL表达能否对共移植的胰岛移植物提供免疫豁免作用以及胰岛细胞FasL基因转染对同种胰岛移植的影响.方法将同种大鼠胰岛及睾丸细胞同时移植于糖尿病受体,重组腺病毒AdV-FasL感染胰岛细胞后移植,观察移植物存活情况、胰岛功能,并检测移植物内浸润淋巴细胞以及基因转染胰岛细胞凋亡情况.结果单纯移植胰岛组平均存活期为(6.3±0.56)?d.与胰岛细胞同时移植的睾丸细胞数增加至1×107时,存活期大于50?d(P＜0.05).表达FasL的睾丸细胞在移植物内诱导浸润淋巴细胞凋亡.FasL基因转染组出现排斥加速,存活期缩短至(3.4±0.24)?d.FasL转染的胰岛细胞在移植后24h见FasL表达,48h表达增强,移植后FasL转染胰岛细胞凋亡.结论表达FasL的睾丸细胞与胰岛同时移植可诱导活化的淋巴细胞凋亡,使胰岛移植物获得免疫豁免、存活期延长,但通过FasL基因转染使胰岛细胞直接表达FasL引起胰岛细胞凋亡和粒细胞浸润,导致排斥加速.     

紫杉醇诱导急性胰腺炎大鼠胰腺腺泡细胞凋亡机制的研究

目的研究急性胰腺炎时紫杉醇诱导大鼠胰腺腺泡细胞凋亡的机制。方法利用胆胰管内注射脱氧胆酸钠的方法建立急性胰腺炎大鼠模型 ,并向腹腔内注射紫杉醇以诱导胰腺腺泡细胞凋亡。利用免疫组化法研究胰腺腺泡细胞凋亡相关蛋白Bcl 2、Bax、Fas、FasL及 p5 3表达的变化。结果急性胰腺炎时大鼠胰腺腺泡细胞中Bax(2 5 0 6± 94 2 )、Fas(2 79± 15 0 )和 p5 3(180± 5 6 )的表达增加 ,Bcl 2 (79± 4 2 )表达无明显变化 ,而FasL只表达于急性胰腺炎时胰腺间质浸润的炎性细胞中。结论急性胰腺炎时紫杉醇诱导的大鼠胰腺腺泡细胞凋亡与Bax、Fas/FasL系统以及p5 3蛋白有关。     

供体脾脏对大鼠移植胰腺转化生长因子-β1mRNA表达的影响

目的观察供体脾脏对胰腺移植免疫反应的影响.方法制作异基因大鼠胰、脾、十二指肠移植模型,观察供体胰腺的病理学变化,测定供体胰腺组织中转化生长因子(TGF)-β1 mR-NA的表达、CD4+和CD8+T淋巴细胞的变化.结果胰、脾、十二指肠移植组(A组)术后3 d胰腺小叶间质、腺泡和胰岛轻度水肿;5 d炎细胞浸润,腺泡细胞灶状坏死;7 d腺泡和胰岛部分坏死、自溶.胰、十二指肠移植组(B组)术后3 d胰腺腺泡片状坏死;5 d胰腺小叶和部分胰岛坏死.7 d腺泡大片坏死,胰岛结构消失.供体胰腺组织中,术后3、5、7 d TGF-β1 mRNA阳性细胞数,A组分别为66.75±8.56、36.50±6.70、36.88±6.06;B组分别为16.38±3.85、10.38±4.03、6.0±2 73.A组术后各时点TGF-β1mRNA的表达均高于B组(P<0.01);结论 TGF-β是减轻受体大鼠对供体胰腺免疫排斥反应的重要因素之一;调高供体胰腺组织TGF-β mRNA的表达是供体脾脏发挥免疫抑制作用的机制之一.     

Fas配体阳性睾丸细胞和环孢素A对移植胰岛细胞存活起协同保护作用

目的　探讨Fas配体 (FasL)阳性睾丸细胞与胰岛细胞共移植后联用环孢素A(CsA)对移植胰岛细胞存活的协同保护作用。　方法　将同种大鼠胰岛细胞与睾丸Sertoli细胞同侧或异侧共移植于 4 1只糖尿病SD大鼠受体肾包膜下。实验大鼠分 7组 ,术后酌用CsA ,观察各组大鼠移植物存活情况。　结果　单纯胰岛细胞移植 (对照组 )后胰岛细胞的平均存活期为 (4 6± 1 1)d ,加用CsA存活期明显延长至 (2 1 8± 4 7)d(P <0 0 1)。与 1× 10 7个睾丸细胞同侧共移植的胰岛细胞平均存活期超过 (5 7 5± 4 0 )d ,但如移植前先封闭睾丸细胞表达的FasL后 ,移植的胰岛细胞平均存活期缩短为(5 8± 2 6 )d。胰岛细胞与 1× 10 5个睾丸细胞分别共移植于两侧肾包膜下 ,术后联用CsA ,胰岛细胞的平均存活期超过 (5 5 0± 6 5 )d ,与 1× 10 7个睾丸细胞同侧共移植的存活期相近 ,但比对照组或CsA组则显著延长 (P <0 0 1)。当胰岛细胞与 1× 10 6个睾丸细胞分别共移植且不用CsA时 ,胰岛细胞存活期平均仅为 (11 5± 3 1)d ,但仍较对照组延长 (P <0 0 5 )。　结论　表达FasL的睾丸细胞与CsA联用后可通过不同机制抑制胰岛细胞移植排斥反应而起到全身的协保护作用。     

Fas/FasL表达和细胞凋亡在大鼠同种异体肝移植免疫中的作用

目的探讨Fas和Fas配体 (fasligand ,FasL)与细胞凋亡在大鼠肝移植免疫中的作用。方法分别用免疫组织化学法及原位杂交法 ,在移植后不同的时间点 (1、3、5、7d)检测Fas FasL、Bcl 2 Bax和细胞凋亡在不同的大鼠肝移植模型中的表达情况。结果肝急性排斥组与自发耐受组相比 ,肝细胞凋亡多 ,汇管区FasL表达高而肝细胞FasL表达低 [(2 1 5± 2 5 )个细胞vs.(39 5± 0 5 )个细胞 ,P <0 0 5 ],并且Fas[(47 0± 8 1)个细胞vs.(14 5± 0 8)个细胞 ,P <0 0 5 ]和Bax[(2 1 4± 1 1)个细胞vs.(9 4± 0 9)个细胞 ,P <0 0 5 ]表达高。子代组与肝急性排斥组各指标表达类似 ,半肝组与自发耐受组各指标表达类似。在移植后第 5天 ,汇管区凋亡指数与肝细胞FasL的表达呈正相关 (r =0 76 0 ,P <0 0 1) ,而与肝细胞Fas(r =- 0 75 9,P <0 0 1)、Bax的表达呈负相关 (r =- 0 840 ,P <0 0 1)。结论肝实质细胞的凋亡与肝急性排斥反应有关 ,而其Fas、Bax的高表达可能介导了肝实质细胞凋亡的发生 ;汇管区浸润细胞凋亡与肝自发耐受有关 ,肝细胞FasL的高表达可能介导了浸润细胞凋亡的发生。     

硒对淋巴细胞杀伤大肠癌细胞过程中Fas/FasL表达的影响

目的　探讨硒对淋巴细胞抗大肠癌过程中凋亡相关基因Fas/FasL表达的影响。方法　以半胱氨酸硒作为影响因素,人T淋巴细胞为效应细胞及人结肠癌细胞（LoVo细胞株）为靶细胞,采用四甲基偶氮唑蓝(MTT)比色法、凋亡细胞荧光计数检测凋亡细胞的数量,逆转录-聚合酶链(RT-PCR)反应、原位杂交技术检测,硒对效应细胞杀伤肿瘤细胞过程中Fas/FasL表达的影响。结果　不同浓度的半胱氨酸硒（0.5、1.0　mg/L）作用48h后,可增强人T淋巴细胞抗肿瘤活性［分别为（25.12±3.91）%,（46.17±3.68）%,P＜0.05］,且肿瘤细胞的凋亡比例上升［分别为(18.6±4.1)%,（32.7±2.1）%,P＜0.05］;能使免疫效应细胞和肿瘤细胞表达FasL和Fas水平增高。结论　硒可提高淋巴细胞的抗肿瘤作用,可能通过Fas/FasL途径起作用。     

中药移植合剂对大鼠胰腺移植急性排斥反应的作用

目的:观察大鼠胰腺移植后的细胞凋亡情况,以及中药移植合剂在急性排斥反应中的作用并探讨其作用机制.方法:建立大鼠全胰十二指肠移植模型,均为异基因移植(以SD、Wistar大鼠作为供、受体),共分5组,每组10只.第1组:阴性对照组;第2组:环孢素A (cyclosporin A, CsA)组,5 mg/(Kg·d);第3组:中药移植合剂组,每100 g体重1 mL/d;第4组:中西医结合组,中药移植合剂每100 g体重1 mL/d CsA 2.5 mg/(Kg·d);第5组:亚治疗剂量CsA组,2.5 mg/(Kg·d).术后第7 d每组处死5只大鼠,取移植胰腺,受体肝脏、肾脏行病理学检查,应用原位末端标记法(TUNEL)检测细胞凋亡情况.余鼠待出现急性排斥反应时处死,观察各组移植胰腺有功能存活时间.结果:中药移植合剂可以延长移植胰腺有功能存活时间,抑制胰腺腺泡细胞凋亡,其与亚治疗剂量CsA合用后可以达到治疗剂量CsA的抗排斥反应效果.结论:中药移植合剂具有一定的抗大鼠胰腺移植急性排斥反应的作用,作用机制与其抑制移植胰腺腺泡细胞凋亡有关,且与CsA具有协同作用.     

胰岛FasL基因转染对大鼠胰岛移植的影响

目的 探究胰岛细胞FasL基因转染对同种大鼠胰岛移植的影响。方法 通过磷酸钙沉淀法构建含目的基因FasL的重组腺病毒AdV-FasL,感染胰岛细胞后移植于糖尿病受者大鼠,通过RT-PCR和免疫组织化学检测移植物FasL表达,观察移植物存活情况及基因转染胰岛细胞凋亡情况。结果 单纯移植胰岛组平均存活期为（6.3±0.56）d,FasL基因转染组并未出现排斥延迟,反而排斥加速,存活期缩短至（3.4±0.24）d。FasL转染的胰岛细胞在移植后24h见FasL表达,在 48 h表达增强,AdV-5感染组及未转染组未见FasL表达。TUNEL标记见移植后FasL转染胰岛细胞凋亡。结论 尽管表达FasL的睾丸细胞与胰岛共移植可诱导活化的淋巴细胞凋亡,使胰岛移植物获得免疫豁免、存活期延长,但通过FasL基因转染使胰岛细胞直接表达FasL,引起胰岛细胞凋亡和粒细胞浸润,导致排斥加速。     

The Fas ligand/Fas system in renal injury.

The FasL-Fas system regulates renal cell apoptosis, as well as the immune and inflammatory responses. Evidence that FasL and Fas participate in renal injury may be summarized along modified Koch's postulates (Table 1): (i) FasL is expressed by renal cells and during renal injury, (ii) activation of the Fas receptor promotes apoptosis of cultured renal cells, (iii) Fas agonists induce glomerular injury but they may also decrease renal injury by limiting injurious immunological responses, (iv) mice with disrupted FasL/Fas systems are protected from tubular cell injury during ischaemia reperfusion, although they develop autoimmune glomerulonephritis if other genetic predisposing factors are present. FasL/Fas must be considered a new target for therapeutic intervention in renal injury. Therapeutic modulation of Fas should aim not only at protecting intrinsic glomerular or tubular epithelial cells from death, but also at modulating the immune, inflammatory, and fibrogenic responses. Possible therapeutic interventions include Fas agonists, soluble Fas receptors, or other antagonists, and targetting of Fas to undesired cells, such as fibroblasts, in order to decrease their numbers in a physiological manner through apoptosis. Any therapeutic attempt should carefully take into account the possible effects of interference with Fas in other 1833 cell systems. Given the complexities of the FasL/Fas system, further studies are warranted.     

Fas/Fas-L信号系统在绝经后骨质疏松症中作用的研究进展

Fas/Fas-L信号系统是外源性凋亡通路的重要组成部分。近年来大量研究发现,Fas/Fas-L信号系统通过诱导细胞凋亡,不仅参与了免疫系统稳态的维持,而且在骨内环境稳态的调节中也发挥了重要的作用。Fas/Fas-L信号系统在不同骨细胞上的表达和分布可能随体内雌激素水平波动而发生变化。当绝经后雌激素分泌不足时,Fas/Fas-L信号系统可通过启动骨细胞外源性凋亡通路,介导成骨和破骨平衡向破骨方向偏移,参与绝经后骨质疏松症的发生发展。通过调节骨细胞上Fas/Fas-L信号系统来平衡破骨细胞骨吸收和成骨细胞骨形成,将为绝经后骨质疏松症的治疗提供新的思路。     

Fas和FasL在胆囊癌免疫逃逸中的作用

目的探讨Fas／FasL在胆囊癌免疫逃逸机制中的作用。方法（1）应用SP免疫组织化学法研究26例胆囊癌组织、18例胆囊腺瘤组织、3例胆囊上皮不典型增生组织和20例慢性胆囊炎组织中Fas蛋白和FasL蛋白的表达水平；（2）运用TUNEL法原位检测在上述4种组织中浸润的淋巴细胞的凋亡。（3）比较在不同的胆囊癌临床病理类型中Fas蛋白和FasL蛋白的表达情况和在原位胆囊癌组织浸润的淋巴细胞的凋亡情况。结果（1）Fas蛋白表达的阳性率在上述4种组织之间的差异无统计学意义。FasL蛋白表达的阳性率在胆囊癌组织显著高于慢性胆囊炎组织（χ^2=4．89。P〈0．05）；（2）浸润的淋巴细胞的凋亡数量在高分化癌显著低于低分化癌（t=2．52，P〈0．05）．在腺瘤和慢性炎症组织中未见到浸润的淋巴细胞的凋亡。（3）浸润的淋巴细胞的数量在腺瘤组织显著低于癌组织（t=6．99，P〈0．01），在慢性炎症组织显著低于腺瘤组织（t=3．66，P〈0．01）：在高分化癌显著低于低分化癌（t=5．31，P〈0．01），在NevinⅠ、Ⅱ、Ⅲ期显著低于Ⅳ、Ⅴ期（t=3．76。P〈0．01）。结论胆囊癌细胞表达的FasL通过诱导在癌组织浸润的淋巴细胞的凋亡从而使癌细胞逃避机体的免疫监视，它的上调表达在胆囊癌的分化、浸润和转移过程中扮演重要角色。     

Fas and Fas ligand expression in cystic fibrosis airway epithelium

BACKGROUND: Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective expression of CFTR protein in epithelial cells. The main cause of mortality in CF is linked to chronic inflammatory and infectious airway processes. Recent studies have suggested perturbations in the apoptotic process in CF cell lines and enterocytes. A study was undertaken to investigate the expression of Fas and Fas ligand (FasL) in CF bronchial epithelium and CF tracheal cell lines. METHODS: Immunohistochemical staining for Fas (alkaline phosphatase anti-alkaline phosphatase) and FasL (immunoperoxidase) was performed in eight CF bronchial epithelial samples and four controls and immunohistochemical DNA fragmentation (TUNEL) was carried out in four CF patients and four controls. Immunofluorescence staining and flow cytometric analysis of Fas and FasL expression was performed in two human tracheal epithelial cell lines (HTEC) with normal and CF genotype. The dosage of serum soluble FasL was examined in 21 patients with CF and 14 healthy volunteers. RESULTS: FasL expression was markedly increased in patients with CF in both the ciliated and submucosal glandular bronchial epithelium compared with controls; Fas was similarly expressed in bronchial samples from controls and CF patients in both the ciliated epithelium and submucosal glands. High levels of DNA fragmentation were observed in CF but with some epithelial cell alterations. Serum concentrations of soluble FasL were frequently undetectable in patients with CF. In vitro, HTEC expressed Fas and FasL in both genotypes. A higher mean fluorescence intensity for FasL expression was noted in CF genotype HTEC with median (range) for six experiments of 74 (25-101) for CF cells and 42 (21-70) for non-CF cells. CONCLUSION: Fas/FasL interaction is probably implicated in the human CF airway apoptotic pathway. The mechanisms of induction of FasL expression and its role in inducing tissue damage or remodelling or in controlling local inflammatory cell apoptosis remain to be determined.     

Expression of Fas and Fas ligand in human testicular germ cell tumours

In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant ( p  < 0.01) increase of the FasL mRNA expression of 21.1 ± 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly ( p  < 0.01) reduced to 0.27 ± 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno-reactivity in six out of eight TGCT samples analysed, while Fas immuno-positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient's age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non-seminomatous TGCT and six age-matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT.     

Prognostic Significance of Fas and Fas Ligand System-Associated Apoptosis in Gastric Cancer

Background: Previous studies indicate that gastric carcinomas express Fas ligand and downregulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated.Methods: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method.Results: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD81 cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD81 cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors.Conclusions: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD81 cells.     

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

BackgroundAn essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas − 670A/G and Fas Ligand (FasL) − 843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients.MethodsIn 47 pediatric kidney transplant recipients and 20 healthy controls, Fas − 670A/G and FasL − 843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured.ResultsSerum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25 ± 298.64 pg/ml vs 143.17 ± 44.55 pg/ml, p = 0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70 ± 279.87 pg/ml vs 507.85 ± 342.80 pg/ml, p = 0.56). Fas − 670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P > 0.05 for all). FasL − 843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P > 0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P = 0.03). FasL − 843C/T alleles were significantly different between patients with and without AR (P = 0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR.ConclusionThis study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR.     

术前化疗对胃癌细胞Fas、FasL表达的影响

Fas属于细胞凋亡信号受体，与其配体FasL（Fas ligand，FasL）结合后诱导Fas所在细胞凋亡。本研究通过术前化疗诱导胃癌凋亡，研究胃癌Fas、FasL表达变化的意义。     

Expression of Fas but not Fas ligand on fetal pig beta cells

BACKGROUND: The aim of this study was to determine whether fetal pig insulin-producing cells, a potential source of transplantable tissue for the treatment of type 1 diabetes, are affected by the Fas-FasL interaction, one of the cytotoxic pathways involved in T-cell-mediated autoimmune destruction of pancreatic beta cells. METHODS: Expression of Fas/FasL on fetal pig beta cells was assessed by immunohistochemistry, flow cytometry, Western blot, and RT-PCR. Apoptosis of fetal pig beta cells induced by soluble FasL (sFasL) or anti-Fas antibody (APO-1) was detected by flow cytometry using PI. Expression of FLIP on fetal pig pancreatic tissue was detected by immunofluorescent staining and Western blot. RESULTS: Fas was expressed on fetal pig pancreatic cells, both beta and non-beta cells, and the level of expression could be upregulated by exposure to human interleukin-1beta (IL1beta) 2000 pg/ml for 24 h. In contrast, FasL was not detected on fetal pig pancreatic cells but could be induced on both beta and non-beta cells when the cells were treated with IL1beta. Fas persisted on fetal pig beta cells transplanted as islet-like cell clusters into severe combined immunodeficient mice, with expression of this antigen at all times examined, 1 day, 2, 3 and 4 weeks. FasL was absent. Despite the presence of Fas on fetal pig beta cells, addition of sFasL or anti-Fas antibody failed to induce apoptosis of the fetal pig beta cells. In contrast, pig lymphocytes, which express Fas, were destroyed by addition of both sFasL and APO-1. A possible reason for this is the expression on the fetal pig pancreatic cells of FLIP, an inhibitor of Fas-induced apoptosis. CONCLUSIONS: Fetal pig beta cells are resistant to Fas-FasL destruction. Our data imply that fetal pig beta cells transplanted into humans with type 1 diabetes may not be destroyed by activated T cells through the Fas-FasL-mediated pathway.