The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo
The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo
复制标题
DOI：
10.1189/jlb.1103573
复制
发表时间：
2005-01-01
影响因子：
5.5
通讯作者：
Norman, KE
中科院分区：
文献类型：
--
作者：
Hicks, AER;Abbitt, KB;Norman, KE
选择素及其配体支持白细胞滚动，促进炎症期间发生的随后的牢固粘附和迁移。TBC-1269（Bimosiamose）是天然选择素配体的结构模拟物，在体外抑制P-、E-和L-选择素，在体内具有抗炎作用，最近进行了儿童哮喘和银屑病的11期临床试验。我们研究了TBC-1269的抗炎作用是否与体内白细胞滚动有关。尽管TBC-1269在体外抑制鼠白细胞系对鼠P-选择素的滚动，在体内抑制巯基乙酸盐诱导的腹膜炎，但它并不改变小鼠提睾肌小静脉中的白细胞滚动。TBC-1269减少了野生型和P-选择素-/-小鼠中巯基乙酸盐诱导的腹膜炎中的中性粒细胞募集，但在E-选择素-/-小鼠中没有。我们认为TBC-1269的体内作用可能是通过E-选择素介导的，但似乎不涉及白细胞滚动。
Selectins and their ligands support leukocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC-1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P-, E-, and L-selectin in vitro, has anti-inflammatory effects in vivo, and recently underwent phase 11 clinical trials for childhood asthma and psoriasis. We studied whether the anti-inflammatory effects of TBC-1269 could be related to leukocyte rolling in vivo. Although TBC-1269 inhibited rolling of a murine leukocyte cell line on murine P-selectin in vitro and thioglycollate-induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC-1269 reduced neutrophil recruitment in thioglycollate-induced peritonitis in wild-type and P-selectin-/- mice but not in E-sclectin-/- mice. We suggest that the in vivo effects of TBC-1269 may be mediated through E-selectin but do not appear to involve leukocyte rolling.