Pasteurella multocida Toxin-Stimulated Osteoclast Differentiation Is B Cell Dependent
Pasteurella multocida Toxin-Stimulated Osteoclast Differentiation Is B Cell Dependent
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DOI：
10.1128/iai.00565-10
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发表时间：
2011-01-01
影响因子：
3.1
通讯作者：
Kubatzky, Katharina F.
中科院分区：
文献类型：
--
作者：
Hildebrand, Dagmar;Heeg, Klaus;Kubatzky, Katharina F.
多杀性巴氏杆菌是一种革兰氏阴性杆菌，感染许多野生动物和家畜，引起呼吸道疾病。产毒素多杀性巴氏杆菌菌株产生蛋白毒素（PMT），由于破骨细胞生成增强和成骨细胞功能抑制，导致猪萎缩性鼻炎。我们发现PMT诱导的破骨细胞生成是由尚未表征的B细胞群促进的。然而，该毒素并不作用于造血干细胞水平，因为用PMT培养的鼠造血祖细胞的纯化的CD 117（+）细胞并不成熟为破骨细胞。该细胞群中包含的早期巨噬细胞（CD 117（+）/CD 11b（+））没有进一步分化为破骨细胞，但存活下来并能够吞噬。然而，在CD 117（-）细胞群中，我们检测到PMT诱导产生的B220（+）/CD 19（+）和B220（+）/IgM（+）B细胞群能够摄取荧光标记的PMT。使用纯化的B细胞和巨噬细胞群体，我们表明，这些B细胞需要有效地产生破骨细胞从巨噬细胞。免疫系统的细胞被认为通过分泌细胞因子和生长因子来影响破骨细胞的形成和功能。我们在此表明，与通过与IL-7孵育产生的B细胞相比，PMT刺激的B细胞产生破骨细胞生成因子白细胞介素-1 β（IL-1 β）、IL-6、肿瘤坏死因子α和核因子受体配体的受体激活因子（RANKL）水平升高。这些结果表明，PMT的骨细胞特性可能是由于骨细胞和淋巴细胞之间的串扰，B细胞可能是多杀性巴氏杆菌的一个重要目标。
Pasteurella multocida is a Gram-negative bacillus that infects a number of wild and domestic animals, causing respiratory diseases. Toxigenic Pasteurella multocida strains produce a protein toxin (PMT) that leads to atrophic rhinitis in swine due to enhanced osteoclastogenesis and the inhibition of osteoblast function. We show that PMT-induced osteoclastogenesis is promoted by an as-yet-uncharacterized B-cell population. The toxin, however, is not acting at the level of hematopoietic stem cells, since purified CD117(+) cells from murine hematopoietic progenitor cells cultivated with PMT did not mature into osteoclasts. The early macrophages contained within this cell population (CD117(+)/CD11b(+)) did not further differentiate into osteoclasts but survived and were able to phagocytose. Within the CD117(-) population, however, we detected PMT-induced generation of a B220(+)/CD19(+) and B220(+)/IgM(+) B-cell population that was able to take up fluorescently labeled PMT. Using purified B-cell and macrophage populations, we show that these B cells are needed to efficiently generate osteoclasts from macrophages. Cells of the immune system are thought to affect osteoclast formation and function by secreting cytokines and growth factors. We show here that PMT-stimulated B cells produce elevated levels of the osteoclastogenic factors interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and receptor activator of nuclear factor receptor ligand (RANKL) compared to B cells generated through incubation with IL-7. These results suggest that the osteoclastic properties characteristic for PMT may result from a cross talk between bone cells and lymphoid cells and that B cells might be an important target of Pasteurella multocida.