Zoukhri D, Hodges R R, Rawe I M, Dartt D A
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, 02114, USA.
Clin Immunol Immunopathol. 1998 Nov;89(2):134-40. doi: 10.1006/clin.1998.4598.
Innervation of the lacrimal gland of MRL/Mp-Fas-lpr/lpr (MRL/lpr), a murine model for Sjögren's syndrome, is unaltered with the onset or progression of the lymphocytic infiltration. To determine whether lacrimal and submandibular gland cells are able to respond to external stimuli, acini were prepared from MRL/lpr (diseased) and MRL/Mp-+/+ (MRL/+, control) mice at 4, 8, and 12 weeks of age and loaded with the fluorescent dye fura-2 to monitor changes in the intracellular Ca2+ concentration ([Ca2+]i) in response to cholinergic and alpha1-adrenergic stimulation, two major stimuli of lacrimal gland protein secretion. Cholinergic-induced [Ca2+]i increase was up-regulated 3- and 4-fold in lacrimal gland acini isolated from 8- and 12-week-old MRL/lpr mice, respectively, compared to 4-week-old animals, but was not up-regulated in age-matched MRL/+ control mice. Similarly, alpha1-adrenergic-induced [Ca2+]i increase was up-regulated 7- and 12-fold in acini isolated from 8- and 12-week-old MRL/lpr mice, respectively, compared to 4-week-old animals, but was not up-regulated in MRL/+ mice. Cholinergic-induced [Ca2+]i increase in submandibular gland acini of MRL/lpr and MRL/+ mice was the same at all ages. In contrast, alpha1-adrenergic-induced [Ca2+]i increase was up-regulated 3-fold in acini from 12-week-old MRL/lpr mice, compared to 4-week-old mice, but was not up-regulated in age-matched MRL/+ mice. We conclude that the Ca2+ signaling portion of cholinergic and alpha1-adrenergic pathway in the lacrimal gland and the Ca2+ signaling portion of alpha1-adrenergic pathway in the submandibular gland is up-regulated with the onset and progression of the lymphocytic infiltration in the MRL/lpr murine model of Sjögren's syndrome.
MRL/Mp-Fas-lpr/lpr（MRL/lpr）小鼠是干燥综合征的一种小鼠模型，其泪腺的神经支配不会随着淋巴细胞浸润的发生或进展而改变。为了确定泪腺和颌下腺细胞是否能够对外界刺激作出反应，在4周、8周和12周龄时从MRL/lpr（患病）小鼠和MRL/Mp-+/+（MRL/+，对照）小鼠中分离出腺泡，并用荧光染料fura-2加载，以监测细胞内Ca2+浓度（[Ca2+]i）对胆碱能和α1-肾上腺素能刺激（泪腺蛋白分泌的两种主要刺激）的变化。与4周龄动物相比，从8周龄和12周龄MRL/lpr小鼠分离出的泪腺腺泡中，胆碱能诱导的[Ca2+]i增加分别上调了3倍和4倍，但在年龄匹配的MRL/+对照小鼠中未上调。同样，与4周龄动物相比，从8周龄和12周龄MRL/lpr小鼠分离出的腺泡中，α1-肾上腺素能诱导的[Ca2+]i增加分别上调了7倍和12倍，但在MRL/+小鼠中未上调。MRL/lpr和MRL/+小鼠颌下腺腺泡中胆碱能诱导的[Ca2+]i增加在所有年龄段都是相同的。相比之下，与4周龄小鼠相比，12周龄MRL/lpr小鼠腺泡中α1-肾上腺素能诱导的[Ca2+]i增加上调了3倍，但在年龄匹配的MRL/+小鼠中未上调。我们得出结论，在干燥综合征的MRL/lpr小鼠模型中，随着淋巴细胞浸润的发生和进展，泪腺中胆碱能和α1-肾上腺素能途径的Ca2+信号部分以及颌下腺中α1-肾上腺素能途径的Ca+信号部分上调。
