Paape Max, Mehrzad Jalil, Zhao Xin, Detilleux Johann, Burvenich Christian
Immunology and Disease Resistance Laboratory, Building 1040, USDA-ARS, Beltsville 29705, Maryland, USA.
J Mammary Gland Biol Neoplasia. 2002 Apr;7(2):109-21. doi: 10.1023/a:1020343717817.
The primary phagocytic cells of the bovine mammary gland, polymorphonuclear neutrophil leukocytes (PMN), and macrophages, comprise the first line of defense against invading pathogens. In the normal healthy mammary gland, macrophages predominate and act as sentinels to invading mastitis-causing pathogens. Once invaders are detected, macrophages, and possibly mammary epithelial cells, release chemoattractants that direct migration of PMN into the area. In the mammary gland, protection is only effective if rapid influx of PMN from the circulation and subsequent phagocytosis and killing of bacteria occur. The second line of defense against infection consists of a network of memory cells and immunoglobulins that interact with the first line of defense. To minimize mammary tissue damage caused by bacterial toxins and oxidative products released by PMN, elimination of invading bacteria must proceed quickly. Therefore, the inflammatory response needs to be regulated. Hormones, metabolites, and acute phase proteins act to influence the outcome of mastitis, especially around parturition. The number of circulating PMN in cows during early lactation is highly heritable and closely related to susceptibility to clinical mastitis at this time. Advances in molecular biology are making available the tools, techniques, and products to study and modulate host-pathogen interactions. For example, the cloning and expression of proteins such as recombinant bovine soluble (rbos) CD (cluster of differentiation) 14 antigens, may provide ways of minimizing damaging effects of endotoxin during acute coliform mastitis. Soluble CD14 binds and neutralizes lipopolysacharide (LPS) and causes local recruitment of PMN after binding of CD14-LPS complexes to mammary epithelial cells. Development of transgenic animals that express rbosCD14 in their milk could prevent infection by Gram-negative pathogens.
牛乳腺的主要吞噬细胞,即多形核嗜中性白细胞(PMN)和巨噬细胞,构成了抵御入侵病原体的第一道防线。在正常健康的乳腺中,巨噬细胞占主导地位,并作为入侵乳腺炎病原体的哨兵。一旦检测到入侵者,巨噬细胞以及可能的乳腺上皮细胞会释放趋化因子,引导PMN迁移到该区域。在乳腺中,只有当PMN从循环中快速涌入并随后吞噬和杀灭细菌时,保护才有效。抵御感染的第二道防线由记忆细胞和免疫球蛋白网络组成,它们与第一道防线相互作用。为了将PMN释放的细菌毒素和氧化产物对乳腺组织造成的损害降至最低,必须迅速清除入侵细菌。因此,炎症反应需要得到调节。激素、代谢产物和急性期蛋白会影响乳腺炎的结果,尤其是在分娩前后。奶牛在泌乳早期循环PMN的数量具有高度遗传性,并且与此时临床乳腺炎的易感性密切相关。分子生物学的进展为研究和调节宿主 - 病原体相互作用提供了工具、技术和产品。例如,重组牛可溶性(rbos)CD(分化簇)14抗原等蛋白质的克隆和表达,可能提供在急性大肠杆菌性乳腺炎期间将内毒素的破坏作用降至最低的方法。可溶性CD14结合并中和脂多糖(LPS),并在CD14 - LPS复合物与乳腺上皮细胞结合后引起PMN的局部募集。在其乳汁中表达rbosCD14的转基因动物的培育可以预防革兰氏阴性病原体的感染。