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

比较了白细胞黏附缺陷母牛补体受体3(CR3)缺乏的中性粒细胞的免疫球蛋白G介导的吞噬功能、超氧化物生成和细胞内钙([Ca~(2+)]_i)信号。包被免疫球蛋白的酵母菌和聚集的牛免疫球蛋白(Agg-IgG)诱导的CR3缺陷性中性粒细胞的平均吞噬活性分别是对照组的10%和77.9%。经Agg-Ig G或刀豆蛋白A刺激的CR3缺陷性中性粒细胞[Ca~(2+)]_i信号缺乏，[Ca~(2+)]~(2+)平均峰值浓度分别为对照组的78%和42%。这些结果表明，Fc受体介导的中性粒细胞功能与中性粒细胞表面CR3的存在密切相关。B2整合素缺乏症(BLAD)小牛白细胞向…的迁移与正常小腿相比，小腿间隙和刮除的组织更多。在患BLAD的小牛的支气管肺泡灌洗液中发现了中性粒细胞，表现为慢性肺炎。用抗CD18单抗进行流式细胞术分析，中性粒细胞CR3阴性。从小牛支气管肺泡灌洗液中分离的中性粒细胞中，CR3介导的化学发光反应与CR3缺乏的中性粒细胞相似。用皮肤窗法检测正常小牛的中性粒细胞迁移到刮除的组织中。这些发现证实了正常和CR3缺乏的中性粒细胞渗入刮除组织的特性。对一头患有BLAD的8个月龄小母牛进行了颗粒细胞输注，以监测B2整合素缺陷宿主输入的CD18阳性中性粒细胞的变化和相关的中性粒细胞化学发光反应。在GT后的前3小时，血中检测到CD18阳性的中性粒细胞，并在GT后5小时消失。在GT后的前3小时，布莱德小母牛的中性粒细胞的CL反应增加了1.7~2.8倍，此后在GT后2~5小时，中性粒细胞的CL反应逐渐降低。对一头9个月龄的BLAD母牛进行了骨髓移植(BMT)。骨髓移植后12个月，在流式细胞仪的CD18阳性区域显示一个小的荧光区，估计占免疫磁分离后的流式细胞仪分析的CD18阳性中性粒细胞的0.3-0.5%。在BMT后28个月的观察期内，动物的临床情况似乎有所改善和稳定。新表达的CD18似乎在改善这头小母牛BLAD的临床症状方面发挥了重要作用。较少

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