Modulation of T lymphocyte function by the angiogenesis inhibitor AGM-1470.
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.
Berger
A E
AE
Upjohn Laboratories, Kalamazoo, MI 49007.
Dortch
K A
KA
Staite
N D
ND
Mitchell
M A
MA
Evans
B R
BR
Holm
M S
MS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002478:Cells, Cultured; D003510:Cyclohexanes; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D013208:Staphylococcal Toxoid / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013744:Tetanus Toxin / Q000633:toxicity
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D007376:Interleukin-2; D012717:Sesquiterpenes; D013208:Staphylococcal Toxoid; D013744:Tetanus Toxin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol