Hicks Anne E R, Abbitt Kate B, Dodd Paul, Ridger Victoria C, Hellewell Paul G, Norman Keith E
Cardiovascular Research Unit, University of Sheffield, United Kingdom.
J Leukoc Biol. 2005 Jan;77(1):59-66. doi: 10.1189/jlb.1103573. Epub 2004 Oct 5.
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 II 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-selectin-/- 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.
选择素及其配体支持白细胞滚动，促进炎症过程中随后发生的牢固黏附和迁移。TBC-1269（比莫司胺）是天然选择素配体的结构模拟物，在体外可抑制P-、E-和L-选择素，在体内具有抗炎作用，最近已针对儿童哮喘和银屑病进行了II期临床试验。我们研究了TBC-1269的抗炎作用是否可能与体内白细胞滚动有关。尽管TBC-1269在体外抑制了小鼠白细胞系在小鼠P-选择素上的滚动以及在体内抑制了巯基乙酸诱导的腹膜炎，但它并未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-选择素基因敲除小鼠中巯基乙酸诱导的腹膜炎中的中性粒细胞募集，但在E-选择素基因敲除小鼠中则没有。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。
