Berger A E, Dortch K A, Staite N D, Mitchell M A, Evans B R, Holm M S
Upjohn Laboratories, Kalamazoo, MI 49007.
Agents Actions. 1993;39 Spec No:C86-8. doi: 10.1007/BF01972729.
The angiogenesis inhibitor AGM-1470 has recently been reported to inhibit collagen-induced arthritis in rats. To determine if the anti-arthritic effects of AGM-1470 might be due to T cell inhibition, we have studied its effects on T cell responses in vitro. Responses of human cells to tetanus toxoid (TT), and those of murine splenocytes to staphylococcal enterotoxin (SE), mitogens or a mls difference were inhibited by AGM-1470. Responses of human cells to SE, OKT3 and PHA were all partially inhibited on day 2 (d2) but not d3, and in fact were augmented on d6-8. The amount of IL-2 in SEA cultures was augmented on d4 and d5. There were no differences in the expression of CD3, CD4, CD8, CD25, CD45RA, CD45RO, LFA-1, VLA-4 or VLA-6 in inhibited cultures, except for slight decreases in CD25 and CD45RO in TT cultures. These results indicated that the angiogenesis inhibitor AGM-1470 also modulates human and murine lymphocyte function.
血管生成抑制剂AGM - 1470最近被报道可抑制大鼠胶原诱导的关节炎。为了确定AGM - 1470的抗关节炎作用是否可能归因于T细胞抑制,我们研究了其对体外T细胞反应的影响。AGM - 1470抑制了人细胞对破伤风类毒素(TT)的反应以及小鼠脾细胞对葡萄球菌肠毒素(SE)、丝裂原或微小淋巴细胞刺激决定簇差异的反应。人细胞对SE、OKT3和PHA的反应在第2天(d2)均受到部分抑制,但在第3天未受抑制,实际上在第6 - 8天有所增强。在SEA培养物中,IL - 2的量在第4天和第5天增加。在受抑制的培养物中,CD3、CD4、CD8、CD25、CD45RA、CD45RO、LFA - 1、VLA - 4或VLA - 6的表达没有差异,除了TT培养物中CD25和CD45RO略有下降。这些结果表明血管生成抑制剂AGM - 1470也调节人和小鼠淋巴细胞的功能。