Effects of the anti-inflammatory compounds castanospermine, mannose-6-phosphate and fucoidan on allograft rejection and elicited peritoneal exudates.
The glycoprotein processing inhibitor castanospermine (CS) and the monosaccharide mannose-6-phosphate (M6P), as well as some sulfated polysaccharides (SPS), have been shown to inhibit inflammation in rat models of experimental autoimmune encephalomyelitis and adjuvant-induced arthritis. Here, the anti-inflammatory effects of these agents have been further explored in murine models of allograft rejection and elicitation of peritoneal exudates. CS, M6P and the SPS, fucoidan, partially inhibited rejection of permanently accepted thyroid allografts induced by the i.p. injection of donor strain (H-2d) spleen cells with a reduction in leucocyte infiltration of 25-36%. However none of these agents reduced the more extensive leucocyte infiltration induced by the i.p. injection of P815 (H-2d) unless recipient mice were pretreated with the immunosuppressant, cyclosporin A (CsA). Elicitation of peritoneal exudates by thioglycollate was inhibited by CS, M6P and fucoidan with sustained leucopenia being induced by CS. In contrast, CS and fucoidan, but not M6P, inhibited antigen-elicited peritoneal exudates. These results suggest that CS, M6P and the SPS fucoidan exhibit subtle differences in their anti-inflammatory activity but probably inhibit inflammation at the level of leucocyte extravasation.
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
M R
MR
Bartlett
H S
HS
Warren
W B
WB
Cowden
C R
CR
Parish
D000818:Animals; D001202:Ascitic Fluid / Q000139:chemically induced / Q000517:prevention & control*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D007212:Indolizines / Q000494:pharmacology*; D008297:Male; D008360:Mannosephosphates / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008954:Models, Biological; D009368:Neoplasm Transplantation; D011134:Polysaccharides / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013864:Thioglycolates / Q000633:toxicity; D013961:Thyroid Gland / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous; D054836:Indolizidines
D016572:Cyclosporine; D005959:Glucosidases; D007212:Indolizines; D008360:Mannosephosphates; D011134:Polysaccharides; D013864:Thioglycolates; C027693:mannose-6-phosphate; C007789:fucoidan; C037806:castanospermine; D054836:Indolizidines