Hall L R, Lass J H, Diaconu E, Strine E R, Pearlman E
Division of Geographic Medicine, Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, OH 44106, USA.
J Immunol. 1999 Nov 1;163(9):4970-5.
Invasion of the corneal stroma by neutrophils and eosinophils and subsequent degranulation disrupts corneal clarity and can result in permanent loss of vision. In the current study, we used a model of helminth-induced inflammation to demonstrate a novel role for Ab in mediating recruitment of these inflammatory cells to the central cornea. C57BL/6 and B cell-deficient (microMT) mice were immunized s. c. and injected intrastromally with Ags from the parasitic helminth Onchocerca volvulus (which causes river blindness). C57BL/6 mice developed pronounced corneal opacification, which was associated with an Ag-specific IL-5 response and peripheral eosinophilia, temporal recruitment of neutrophils and eosinophils from the limbal vessels to the peripheral cornea and subsequent migration to the central cornea. In contrast, the corneas of microMT mice failed to develop keratitis after intrastromal injection of parasite Ags unless Ags were injected with immune sera. Eosinophils were recruited from the limbal vessels to the peripheral cornea in microMT mice, but failed to migrate to the central cornea, whereas neutrophil recruitment was impaired at both stages. With the exception of IL-5, T cell responses and peripheral eosinophils were not significantly different between C57BL/6 and microMT mice. Taken together, these findings not only demonstrate that Ab is required for the development of keratitis, but also show that recruitment of neutrophils to the cornea is Ab-dependent, whereas eosinophil migration is only partially dependent upon Ab interactions.
中性粒细胞和嗜酸性粒细胞侵入角膜基质并随后脱颗粒会破坏角膜透明度,可能导致永久性视力丧失。在本研究中,我们使用了一种蠕虫诱导的炎症模型来证明抗体在介导这些炎症细胞向角膜中央募集方面的新作用。对C57BL/6和B细胞缺陷(microMT)小鼠进行皮下免疫,并向角膜基质内注射来自寄生蠕虫盘尾丝虫(导致河盲症)的抗原。C57BL/6小鼠出现明显的角膜混浊,这与抗原特异性IL-5反应和外周嗜酸性粒细胞增多、中性粒细胞和嗜酸性粒细胞从角膜缘血管向周边角膜的暂时性募集以及随后向角膜中央的迁移有关。相比之下,microMT小鼠在角膜基质内注射寄生虫抗原后未发生角膜炎,除非抗原与免疫血清一起注射。在microMT小鼠中,嗜酸性粒细胞从角膜缘血管募集到周边角膜,但未能迁移到角膜中央,而中性粒细胞在两个阶段的募集均受损。除IL-5外,C57BL/6和microMT小鼠的T细胞反应和外周嗜酸性粒细胞无显著差异。综上所述,这些发现不仅证明抗体是角膜炎发生所必需的,而且表明中性粒细胞向角膜的募集依赖于抗体,而嗜酸性粒细胞的迁移仅部分依赖于抗体相互作用。