Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Allergy. 2011 Mar;66(3):376-85. doi: 10.1111/j.1398-9995.2010.02494.x. Epub 2010 Oct 26.
Mast cells (MCs) and eosinophils (Eos) are the key effector cells of the allergic reaction. Although classically associated with different stages of the response, the cells co-exist in the inflamed tissue in the late and chronic phases in high numbers and are likely to cross-talk. While some mediators of MCs are known to affect Eos biology and vice versa, paracrine and physical interplay between the two cells has not been described yet. We aimed to investigate whether intercellular MC-Eos communication could take place in the allergic response and exert functional bidirectional changes on the cells.
Tissue sections from various allergic disorders were specifically stained for both cells. Human cord blood-derived MCs and peripheral blood Eos, co-cultured under different conditions, were studied by advanced microscopy and flow cytometry.
Several co-localized MC-Eos pairs were detected in human nasal polyps and asthmatic bronchi, as well in mouse atopic dermatitis. In vitro, MCs and Eos formed stable conjugates at high rates, with clear membrane contact. In the presence of MCs, Eos were significantly more viable under several co-culture conditions and at both IgE-activated and steroid-inhibited settings. MC regulation of Eos survival required communication through soluble mediators but was even more dependent on physical cell-cell contact.
Our findings provide the first evidence for a complex network of paracrine and membrane interactions between MCs and Eos. The prosurvival phenotype induced by this MC-Eos interplay may be critical for sustaining chronic allergic inflammation.
肥大细胞(MCs)和嗜酸性粒细胞(Eos)是过敏反应的关键效应细胞。尽管它们与反应的不同阶段有关,但在晚期和慢性阶段,大量的细胞在炎症组织中共存,并可能发生串扰。虽然已知 MCs 的一些介质会影响 Eos 生物学,反之亦然,但这两种细胞之间的旁分泌和物理相互作用尚未被描述。我们旨在研究细胞间 MC-Eos 通讯是否可以在过敏反应中发生,并对细胞产生功能双向变化。
专门对各种过敏疾病的组织切片进行两种细胞的特异性染色。在不同条件下共培养人脐带血衍生的 MC 和外周血 Eos,通过高级显微镜和流式细胞术进行研究。
在人类鼻息肉和哮喘支气管以及过敏性皮炎的小鼠中检测到了几个共定位的 MC-Eos 对。在体外,MC 和 Eos 以高比率形成稳定的共轭物,具有明显的膜接触。在 MC 的存在下,在几种共培养条件下,Eos 在 IgE 激活和类固醇抑制的情况下,其活力明显更高。MC 对 Eos 存活的调节需要通过可溶性介质进行通讯,但更依赖于物理细胞-细胞接触。
我们的研究结果为 MC 和 Eos 之间的旁分泌和膜相互作用的复杂网络提供了首个证据。这种 MC-Eos 相互作用诱导的生存表型对于维持慢性过敏炎症可能至关重要。