Ackerman K D, Felten S Y, Dijkstra C D, Livnat S, Felten D L
Department of Neurobiology and Anatomy, University of Rochester, School of Medicine and Dentistry, New York 14642.
Exp Neurol. 1989 Mar;103(3):239-55. doi: 10.1016/0014-4886(89)90048-4.
By combining neurochemical measurement of norepinephrine (NE) with double-label immunocytochemistry for tyrosine hydroxylase-positive (TH+) noradrenergic nerves and specific lymphoid markers, we have examined the developmental compartmentation of noradrenergic nerves in the rat spleen. TH+ nerve fibers were present in the white pulp of the spleen at birth, among surface IgM-positive (sIgM+) B lymphocytes at the outer border of the periarteriolar lymphatic sheath (PALS), distant from the central artery. During the first 7 days, noradrenergic innervation developed rapidly, forming plexuses of nerve fibers along the central artery and its branches, among T and B lymphocytes of the PALS, and along the developing marginal sinus where ED3+ macrophages accumulate. The splenic concentration of NE (per mg wet wt.) and 3-methoxy-4-hydroxy-phenetheleneglycol (MHPG), a NE metabolite, increased rapidly during this period, suggesting that NE is available and released from these nerves. From 7-14 days, the white pulp expanded to include an inner PALS, outer PALS, marginal sinus, and marginal zone; during this period, TH+ fibers arborized principally among T lymphocytes of the inner PALS and adjacent to macrophages along the marginal sinus. By 14 days of age, NE concentration reached adult levels, although the MHPG/NE ratio (an index of NE turnover) remained higher throughout development than in adulthood. Finally, from 14-28 days, the outer PALS expanded to include follicles containing sIgM+ B lymphocytes. At the earliest stages of follicular development, a parafollicular rim of noradrenergic fibers was present, providing occasional branches which arborized within the follicle. No further changes were observed in either noradrenergic innervation or cellular compartmentation after 28 days of age. These findings suggest that noradrenergic fibers are present in developing compartments of the spleen at the earliest stages of their development, providing norepinephrine for interaction with a variety of adrenoceptor-bearing lymphoid and nonlymphoid cells.
通过将去甲肾上腺素（NE）的神经化学测量与酪氨酸羟化酶阳性（TH+）去甲肾上腺素能神经和特定淋巴标记物的双标记免疫细胞化学相结合，我们研究了大鼠脾脏中去甲肾上腺素能神经的发育分隔。出生时，TH+神经纤维存在于脾脏白髓中，位于动脉周围淋巴鞘（PALS）外边界的表面IgM阳性（sIgM+）B淋巴细胞之间，远离中央动脉。在最初的7天里，去甲肾上腺素能神经支配迅速发展，沿着中央动脉及其分支、在PALS的T和B淋巴细胞之间以及沿着ED3+巨噬细胞聚集的发育中的边缘窦形成神经纤维丛。在此期间，脾脏中NE（每毫克湿重）和NE代谢物3-甲氧基-4-羟基苯乙二醇（MHPG）的浓度迅速增加，表明NE可从这些神经中获得并释放。从7到14天，白髓扩展至包括内部PALS、外部PALS、边缘窦和边缘区；在此期间，TH+纤维主要在内部PALS的T淋巴细胞中分支，并沿着边缘窦与巨噬细胞相邻。到14日龄时，NE浓度达到成年水平，尽管MHPG/NE比值（NE周转率指标）在整个发育过程中始终高于成年期。最后，从14到28天，外部PALS扩展至包括含有sIgM+ B淋巴细胞的滤泡。在滤泡发育的最早阶段，存在去甲肾上腺素能纤维的滤泡旁边缘，提供偶尔在滤泡内分支的分支。28日龄后，去甲肾上腺素能神经支配或细胞分隔均未观察到进一步变化。这些发现表明，去甲肾上腺素能纤维在脾脏发育的最早阶段就存在于其发育中的分隔中，为与多种带有肾上腺素能受体的淋巴细胞和非淋巴细胞相互作用提供去甲肾上腺素。
