Structure-activity relationship and conformational analysis of monoglycosylceramides on the syngeneic mixed leukocyte reaction.
We examined effects of alpha-, beta-galactosylceramides (CalCers) and alpha-, beta-glucosylceramides (GlcCers) on the syngeneic mixed leukocyte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these alpha-monoglycosylceramides markedly stimulated the proliferation of spleen cells, in contrast to the little stimulatory effects produced by the DC pretreated with the corresponding beta-anomers. In addition, when we compared the effects of alpha-GalCer derivatives on the syngeneic MLR, it appeared that the 2"- and 3-hydroxyl groups in alpha-GalCers play a critical role in their stimulation of the MLR response. Based on these results, we performed a computer-aided molecular modeling study, and found that the orientations of the 2"-, 4"- and 3-hydroxyl groups common to alpha-GalCer and alpha-GlcCer are not accessible to those of inactive monoglycosyleeramides such as beta-GalCer. These results suggest that there might be a receptor-like site for alpha-monoglycosylceramides on the cells which are involved in the MLR response.
Iijima
H
H
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd, Gunma, Japan.
Kimura
K
K
Sakai
T
T
Uchimura
A
A
Shimizu
T
T
Ueno
H
H
Natori
T
T
Koezuka
Y
Y
D000818:Animals; D002236:Carbohydrate Conformation; D002518:Ceramides / Q000737:chemistry* / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005699:Galactosylceramides / Q000737:chemistry / Q000494:pharmacology*; D005963:Glucosylceramides / Q000737:chemistry* / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
C107484:AGL 517; C116527:AGL 563; D002518:Ceramides; D005699:Galactosylceramides; D005963:Glucosylceramides; C103873:KRN 7000