Pathobiology of leukocyte functions from cattle with leukocyte adhesion deficiency(BLAD)and trials of bone marrow transplantation to BLAD-cattle.

白细胞粘附缺陷（BLAD）牛白细胞功能的病理学以及 BLAD 牛骨髓移植试验。

基本信息

批准号：
09660344
负责人：
NAGAHATA Hajime
金额：
$ 2.05万
依托单位：
RAKUNO GAKUEN UNIVERSITY,FACULTY OF VETERINARY MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660344/
关键词：
BLAD TRANSFUSION BONE MARROW TRANSPLANTATION CD18 GENETIC DISEASE TRANSFUSION CATTLE DISEASE

项目摘要

The above-entitled study was performed and the results were summarized as follows :Fc receptor for immunoglobulin G-mediated phagocytosis, superoxide production and intracellular calcium ([Ca^2+]^i) signaling of complement receptor type 3-(CR3) deficient neutrophils from a heifer with leukocyte adhesion deficiency were compared to those of control heifers. The mean phagocytic activity of IgG-coated yeasts and aggregated bovine IgG (Agg-IgG)-induced superoxide production of CR3-deficient neutrophils were 10% and 77.9%, respectively, of those of control neutrophils. The [Ca^2+]^i signals in CR3-deficient neutrophils stimulated with Agg-Igg or concanavalin A were deficient with mean peak [Ca^2+]^i concentrations of 78% and 42% of those of controls. These findings suggest that Fc receptor-mediated neutrophil functions are closely dependent on the presence of CR3 on the neutrophil cell surfaces.The emigration of leukocytes from calves with B2 integrin deficiency (BLAD) into bronchoalveolar … More spaces and scraped tissues was compared to that of normal calves. Neutrophils were found in bronchoalveolar lavage fluid from BLAD-affected calves showing chronic -pneumonia. The neutrophils were CR3-negative when characterized by flow cytometric analysis using anti-CD18 monoclonal antibody. Chemiluminescent response mediated by CR3 in neutrophils isolated from bronchoalveolar lavage fluid from BLAD-calves showed similar findings obtained from CR3-deficient neutrophils. Neutrophils from normal calves migrated to the scraped tissue, evaluated by skin window method. These findings confirmed the extravasating property of normal and CR3-deficient neutrophils into scraped tissues.Granulocyte transfusion as performed in an 8-month-old heifer with BLAD to monitor the changes in transfused CDl8-positive neutrophils and associated neutrophil chemilurninescent response in B2 integrin deficient host. The CD18-positive neutrophils were detected in blood from the BLAD heifer during the first 3 hr after 2.6xl0^9cells were infused by GT, and disappeared by 5 hr after GT.The CL response of neutrophils was increased 1.7 to 2.8-fold in the BLAD heifer during the first 3 hr after GT, thereafter CL response decreased gradually from 2 to 5 hr after GT.Bone marrow transplantation (BMT) was performed in a 9-month-old heifer with BLAD.Clinical and hematological findings, selected neutrophil function and CD18 expression of neutrophils in a B2 integrin-deficient heifer were examined. Twelve months after BMT, a small fluorescent region in the CD18-positive area of a flow cytometric profile was demonstrated and estimated to represent 0.3-0.5% of the CD18-positive neutrophils as measured by flow cytometric analysis following irnmunomagnetic separation. The animal's clinical condition appeared to improve and stabilize over our observation period of 28 months following BMT.Newly expressed CD18 seemed to play an important role in ameliorating the clinical signs of BLAD in this heifer. Less

The above-entitled study was performed and the results were summarized as follows:Fc receptor for immunoglobulin G-mediated phagocytosis, superoxide production and intracellular calcium ([Ca^2+]^i) signaling of complement receptor type 3-(CR3) deficient neutrophils from a heifer with leukocyte adhesive deficiency were compared to those of control heifers. IgG涂层酵母菌和综合的牛IgG（Agg-IgG）诱导的CR3缺乏性中性粒细胞的超氧化物产生的平均吞噬活性分别为10％和77.9％。用Agg-Igg或con菜蛋白A刺激的CR3缺乏性中性粒细胞中的[Ca^2+]^I信号缺乏，平均峰[Ca^2+]^I浓度为78％和42％的对照组。这些发现表明，FC受体介导的嗜中性粒细胞功能紧密取决于白细胞从具有B2整联蛋白缺乏症（Blad）到支气管肺泡的犊牛的迁移中，将更多的空间和刮擦的组织与正常犊牛进行了比较。嗜中性粒细胞在受叶片影响的犊牛的支气管肺泡灌洗液中发现，显示出慢性 - 肾上腺素。当使用抗CD18单克隆抗体的流式细胞术分析表征中性粒细胞Cr3阴性。由CR3介导的化学发光反应从嵌合孔中的支气管肺泡灌洗液分离的中性粒细胞中，显示出从CR3缺乏性嗜中性粒细胞中获得的相似发现。通过皮肤窗方法评估，来自正常犊牛的中性粒细胞迁移到刮擦组织。这些发现证实了正常和CR3缺乏性嗜中性粒细胞在刮擦组织中的外在特性。在具有blad的8个月大的小母牛中进行的粒细胞输血，以监测输血的CDL8阳性中性粒细胞的变化，以及相关的中性粒细胞增生型中性粒细胞化型整合蛋白防御蛋白中的嗜中性粒细胞化学反应。在2.6xl0^9细胞被GT注入2.6xl0^9细胞后，在blad小母牛的血液中检测到CD18阳性嗜中性粒细胞，并在GT后5小时消失。中性粒细胞的Cl响应在GLAD后3 hr中逐渐增加了1.7倍至2.8倍的HER，在GT后，GT逐渐减少了Cl的Marr，在GT后均逐渐减少。在具有膀胱和血液学发现，选定的嗜中性粒细胞功能和中性粒细胞中嗜中性粒细胞的CD18表达中，检查了在9个月大的小母牛中进行移植（BMT）。 BMT十二个月后，证明了流式细胞仪特征的CD18阳性区域中的一个小荧光区域，并估计代表了在IRNMUNOMAGNETIC分离后通过流式细胞仪分析测量的CD18阳性嗜中性粒细胞的0.3-0.5％。在BMT表达CD18后28个月的观察期间，该动物的临床状况似乎改善和稳定，似乎在改善该小母牛的Blad临床迹象方面起着重要作用。较少的