Human Renal Allograft Rejection Despite the Absence of Allogeneic Passenger Leukocytes

Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sister. Eleven years later he developed renal failure. The sister's marrow was noted to be 100% XY karyotype and free of malignancy. She donated a kidney to her brother. Immunosuppression was tapered following transplantation. After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day. A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he presented with severe rejection that reversed with Thymoglobulin. Renal function returned to baseline and has been stable on conventional immunosuppression.     

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO₄) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B₄ (LTB₄), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB₄ concentration in the control ELF (ca. 5×10^–7 M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB₄ in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO₄-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF. The HPLC study showed that the macrophage chemotactic substance in the BALF obtained from NiSO₄-exposed rats was different from complement fragment (C5a) and its MW was estimated to be 10 – 12 kD. Received: 1 December 1993/Accepted: 16 March 1994     

麦胚提取物对辐射损伤修复的实验研究

目的 研究麦胚提取物对小鼠辐射损伤修复的调节和保护作用。方法 采用辐射前或辐射同时饲喂一定量的麦胚提取物，观察小鼠经X射线一次性全身照射后的临床症状、30d存活率、骨髓微核率、外周血白细胞总数在不同时间的变化。结果 与对照组(单纯照射)比较，饲喂麦胚提取物可使小鼠的头面部皮肤、小肠黏膜、肾脏损伤症状得到明显改善；30d存活率为86．17％(P＜0．01)，提高存活率41．79％，保护系数为1．72；骨髓微核率4．62‰；比对照组(12．14‰)降低(P＜0．01)；外周血白细胞总数在7，13，20，30d均显回升(P＜0.05，P＜0．01，P＜0．01，P＜0．01)。结论 麦胚提取物对小鼠辐射损伤修复有一定程度的调节和保护作用，对于辅助肿瘤放射治疗具有重要意义。     

The influence of synovial fibroblasts on the phagocytosis of Staphylococcus by polymorphonuclear cells

Summary It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanis that contribute to the increased susceptiblity of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surfac on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study sugpurified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMB may lead to reduced clearance of bacteria from the joint.     

Secretion and function of the third component of complement (C3) by murine leukocytes.

Our new finding of de novo synthesis and secretion of C3 by both murine peritoneal macrophages and polymorphonuclear leukocytes (PMN) was confirmed by the incorporation of [35S]methionine into C3 molecules and their complete inhibition by cycloheximide. The methods of secretion of C3 from these two types of cells were compared by examining the C3 contents in their culture supernatants. Completely different modes of secretion were observed, i.e. although macrophages synthesize and secrete C3 constitutively, PMN has a mechanism to store the already synthesized C3 in the cell and secrete it in response to stimuli. Protein kinase C (PKC) activators, e.g. 12-O-tetradecanoyl-phorbol 13-acetate, dioctanoyl glycerol, and mezerein, as well as calcium ionophore A23187 stimulate the secretion of C3 from PMN. These results suggest the involvement of PKC and the calmodulin pathway. A very sensitive method for measuring C3 activity was developed which enabled us to show for the first time that C3 secreted by PMN had opsonizing activity and that particles cultured with PMN were phagocytosed effectively.     

Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.     

创伤性休克后血浆黏附分子的变化及不同复苏液的影响

目的　探讨创伤性休克兔中性粒细胞黏附分子CD11b、血清可溶性细胞间黏附分子(sICAM ) 1的动态变化及不同复苏液的影响。方法　 72只创伤性休克模型兔分为 6组 ,林格氏液组按失血量 2倍输入乳酸林格氏液 ,其他各组按 6ml/kg分别输入右旋糖酐 40、70 6代血浆、7.5 %氯化钠和 2 0 %白蛋白。分别采用流式细胞仪、酶联免疫吸附法检测CD11b、sICAM 1表达值。结果　各实验组休克 1hCD11b及sICAM 1表达增高 ,与对照组比较差异有显著性 (P <0 .0 5 ) ,并于12h达最高值 (林格氏液组 85 .6± 12 .1,60 9.3± 10 1.3 ;高渗盐组 77.5± 10 .3 ,5 18.5± 87.2 ;白蛋白组 78.2± 10 .7,5 2 2 .4± 88.3 ;P <0 .0 1)。高渗盐和白蛋白组 2 4、48hCD11b和sICAM 1分别为5 9 .2± 6.9,5 4.6± 5 .9;3 60 .1± 68.4,2 74.4± 40 .1;5 8.9± 6.4,5 5 .0± 5 .8;3 5 2 .6± 65 .3 ,2 70 .2±3 8.2 ,较林格氏液组 (72 .3± 10 .1,65 .8± 8.3 ;5 0 2 .6± 84.5 ,3 42 .4± 63 .1)降低 (P <0 .0 5 ) ;高渗盐和白蛋白组 (8.3 % )复苏 48h动物死亡率较林格氏液组 (4 1.7% )低 (P <0 .0 5 )。结论　创伤性休克时PMNCD11b和sICAM 1表达增加 ;采用 7.5 %氯化钠或 2 0 %白蛋白复苏时表达值及死亡率较乳酸林格氏液低。