Saito N, Yamada Y, Sannohe S, Honda K, Adachi T, Kayaba H, Chihara J
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan 010-8543.
Lung. 2002;180(5):251-63. doi: 10.1007/s004080000099.
Adhesion molecules and C-C chemokines play an important role in the accumulation of eosinophils in allergic inflammation. In the present study, the expression and function of adhesion molecules on eosinophils from asthmatic patients and involvement of RANTES and eotaxin were examined. Eosinophils isolated by the CD16 negative selection method were stimulated with or without RANTES or eotaxin. Expression of b integrins on eosinophils and the functional adherence to recombinant soluble intercellular adhesion molecule-1 (r-sICAM-1)-coated plates were examined. Compared with normal subjects, eosinophils from asthmatic patients showed increased expression of b2 integrins and functional adherence to r-sICAM-1-coated plates. RANTES and eotaxin augmented the functional adherence of eosinophils without a significant upregulation of b2 integrins. Anti-b2 integrin antibody inhibited the augmentative effect on eosinophil adherence of RANTES and eotaxin. Pertussis toxin, wortmannin, and genistein inhibited chemokine-induced adherence. RANTES and eotaxin are closely related to eosinophil accumulation not only as chemotactic agents but also as augmentative agents for eosinophil adherence through involvement in functional eosinophil adherence to ICAM-1 by a possible qualitative change of b2 integrins. Pertussis toxin-sensitive G proteins, PI3 kinase, and tyrosine kinase are involved in signal transduction leading to activation of b2 integrins on eosinophil following stimulation with RANTES and eotaxin.
黏附分子和C-C趋化因子在过敏性炎症中嗜酸性粒细胞的积聚过程中发挥着重要作用。在本研究中，检测了哮喘患者嗜酸性粒细胞上黏附分子的表达及功能，以及RANTES和嗜酸性粒细胞趋化因子（eotaxin）的作用。采用CD16阴性选择法分离出的嗜酸性粒细胞，分别用或不用RANTES或嗜酸性粒细胞趋化因子进行刺激。检测嗜酸性粒细胞上β整合素的表达以及对包被有重组可溶性细胞间黏附分子-1（r-sICAM-1）的平板的功能黏附情况。与正常受试者相比，哮喘患者的嗜酸性粒细胞显示出β2整合素表达增加以及对包被有r-sICAM-1的平板的功能黏附增强。RANTES和嗜酸性粒细胞趋化因子增强了嗜酸性粒细胞的功能黏附，而β2整合素无明显上调。抗β2整合素抗体抑制了RANTES和嗜酸性粒细胞趋化因子对嗜酸性粒细胞黏附的增强作用。百日咳毒素、渥曼青霉素和染料木黄酮抑制趋化因子诱导的黏附。RANTES和嗜酸性粒细胞趋化因子不仅作为趋化剂，而且通过参与嗜酸性粒细胞对ICAM-1的功能性黏附，可能通过β2整合素的定性变化作为嗜酸性粒细胞黏附的增强剂，与嗜酸性粒细胞的积聚密切相关。百日咳毒素敏感的G蛋白、磷脂酰肌醇-3激酶（PI3激酶）和酪氨酸激酶参与了RANTES和嗜酸性粒细胞趋化因子刺激后导致嗜酸性粒细胞上β2整合素激活的信号转导过程。
