Treatment with the alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine reduces the detection of LFA-1 (CD18/CD11a) by monoclonal antibodies.
The antiviral clinical candidate 6-O-butanoyl castanospermine (MDL 28,574), an alpha-glucosidase 1 inhibitor, was examined for its effect on elementary parameters of immune function. It did not affect the mitogenic response of uninfected human mononuclear leukocytes or the detection of a range of cell surface markers, with the exception of the integrin LFA-1 (CD18/CD11a), which was reduced, after cell growth in vitro. The detection of LFA-1 was also reduced on both human and murine cells after oral administration of the compound to xenochimaeric or normal mice, respectively. Altered LFA-1 expression or function may contribute to reduced cell adhesion and the observed reduction in the in vitro allogeneic response by uninfected cells, as well as the previously described prevention of cell conjugate and HIV-induced syncytium formation.
Bridges
C G
CG
MRC Collaborative Centre, London, UK.
Taylor
D L
DL
Kang
M S
MS
Brennan
T M
TM
Tyms
A S
AS
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D001666:Binding Sites, Antibody; D018821:CD18 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007212:Indolizines / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis* / Q000096:biosynthesis* / Q000276:immunology; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous; D054836:Indolizidines
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; C070715:celgosivir; D054836:Indolizidines