Lim Lina H K, Burdick Monica M, Hudson Sherry A, Mustafa Fatimah Bte, Konstantopoulos Konstantinos, Bochner Bruce S
Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
J Immunol. 2006 May 1;176(9):5346-53. doi: 10.4049/jimmunol.176.9.5346.
Basophils have been shown to accumulate in allergic airways and other extravascular sites. Mechanisms responsible for the selective recruitment of basophils from the blood into tissue sites remain poorly characterized. In this study, we characterized human basophil rolling and adhesion on HUVECs under physiological shear flow conditions. Interestingly, treatment of endothelial cells with the basophil-specific cytokine IL-3 (0.01-10 ng/ml) promoted basophil and eosinophil, but not neutrophil, rolling and exclusively promoted basophil adhesion. Preincubation of HUVECs with an IL-3R-blocking Ab (CD123) before the addition of IL-3 inhibited basophil rolling and adhesion, implicating IL-3R activation on endothelial cells. Incubation of basophils with neuraminidase completely abolished both rolling and adhesion, indicating the involvement of sialylated structures in the process. Abs to the beta(1) integrins, CD49d and CD49e, as well as to P-selectin and P-selectin glycoprotein ligand 1, inhibited basophil rolling and adhesion. Furthermore, blocking chemokine receptors expressed by basophils, such as CCR2, CCR3, and CCR7, demonstrated that CCR7 was involved in the observed recruitment of basophils. These data provide novel insights into how IL-3, acting directly on endothelium, can cause basophils to preferentially interact with blood vessels under physiological flow conditions and be selectively recruited to sites of inflammation.
嗜碱性粒细胞已被证明会在过敏性气道和其他血管外部位积聚。负责将嗜碱性粒细胞从血液中选择性募集到组织部位的机制仍未得到充分表征。在本研究中，我们对生理剪切流条件下人嗜碱性粒细胞在人脐静脉内皮细胞（HUVECs）上的滚动和黏附进行了表征。有趣的是，用嗜碱性粒细胞特异性细胞因子IL-3（0.01 - 10 ng/ml）处理内皮细胞可促进嗜碱性粒细胞和嗜酸性粒细胞的滚动，但不促进中性粒细胞的滚动，且专门促进嗜碱性粒细胞的黏附。在添加IL-3之前用IL-3受体阻断抗体（CD123）预孵育HUVECs可抑制嗜碱性粒细胞的滚动和黏附，这表明内皮细胞上的IL-3受体被激活。用神经氨酸酶孵育嗜碱性粒细胞可完全消除滚动和黏附，表明唾液酸化结构参与了该过程。针对β(1)整合素、CD49d和CD49e以及P-选择素和P-选择素糖蛋白配体1的抗体可抑制嗜碱性粒细胞的滚动和黏附。此外，阻断嗜碱性粒细胞表达的趋化因子受体，如CCR2、CCR3和CCR7，表明CCR7参与了观察到的嗜碱性粒细胞募集。这些数据为IL-3如何直接作用于内皮细胞，使嗜碱性粒细胞在生理流动条件下优先与血管相互作用并被选择性募集到炎症部位提供了新的见解。
