Veterinary Physiology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Veterinary Physiology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
J Dairy Sci. 2021 Jun;104(6):6376-6388. doi: 10.3168/jds.2020-20029. Epub 2021 Mar 25.
The intact blood-milk barrier (BMB) prevents an uncontrolled exchange of soluble and cellular components between blood and milk in the mammary gland. It enables the sustainability of the optimal milk composition for the nourishment of the offspring. Endothelial cells, connective tissue, the basal membrane, and mainly the epithelial cells provide the semipermeability of this barrier, allowing only a selective transfer of components necessary for milk production. The epithelial cells are closely connected to each other by different formations, in which the tight junctions are the most critical for separating the milk-containing compartments from the surrounding extracellular fluid and vasculature. During mastitis, the integrity of the BMB is reduced. This facilitates the transfer of immune cells and immune factors such as antibodies from blood into milk. Simultaneously, the transfer of soluble blood constituents without an obvious immune function into milk is promoted. Furthermore, a reduced BMB integrity causes a loss of milk constituents into the blood circulation. Different mechanisms are responsible for the barrier impairment including tight junction opening, but also cell degradation. To promote the cure of mastitis, the targeted manipulation of the BMB permeability may be a tool to optimize the immune function of the mammary gland. An intensified opening of the BMB supports the antibody transfer from blood into milk, which is supposed to increase the contribution of the specific immune system in the immune defense. On the contrary, a fast closure of the BMB during the recovery from mastitis can accelerate the normalization of milk composition and milk yield. Various agents have been experimentally shown to either open (e.g., pathogens and pathogen-associated molecular patterns, several nonsteroidal anti-inflammatory drugs, oxytocin, calcium chelators) or close (e.g., glucocorticoids, nonsteroidal anti-inflammatory drugs, natural anti-inflammatory drugs) the BMB.
完整的血乳屏障 (BMB) 可防止乳腺中血液和乳汁之间可溶性和细胞成分的不受控制交换。它使最佳乳汁成分得以持续存在，从而为后代提供营养。内皮细胞、结缔组织、基底膜以及主要的上皮细胞提供了这种屏障的半透性，仅允许有选择地转移生产乳汁所需的成分。上皮细胞通过不同的形成方式紧密相连，其中紧密连接对于将含乳隔室与周围细胞外液和脉管系统分隔开最为关键。在乳腺炎期间，BMB 的完整性降低。这促进了免疫细胞和免疫因子（如抗体）从血液向乳汁的转移。同时，促进了无明显免疫功能的可溶性血液成分向乳汁的转移。此外，BMB 完整性的降低会导致乳成分向血液循环中的流失。包括紧密连接开放在内的不同机制负责屏障损伤，但也有细胞降解。为了促进乳腺炎的治愈，靶向操纵 BMB 通透性可能是优化乳腺免疫功能的一种工具。BMB 的强化开放有助于抗体从血液向乳汁转移，这有望增加特异性免疫系统在免疫防御中的贡献。相反，在乳腺炎恢复期间 BMB 的快速关闭可以加速乳汁成分和产奶量的正常化。已经有实验表明，各种药物可通过打开（例如病原体和病原体相关分子模式、几种非甾体抗炎药、催产素、钙螯合剂）或关闭（例如糖皮质激素、非甾体抗炎药、天然抗炎药）BMB。
