Phosphatidylinositol mannosides: synthesis and suppression of allergic airway disease.
Phosphatidylinositol mannoside (PIM) extracts from mycobacteria have been shown previously to suppress allergic airway inflammation in mice. To help determine the structural requirements for activity, PIM1(2) (1), PIM1(6) (2) and PIM2 (3) were synthesized and tested for their ability to suppress cellular inflammation in a mouse model of allergic asthma. The synthetic PIMs were all effective in suppressing airway eosinophilia in the asthma model, with PIM1(6) being the most effective. Suppression of all inflammatory cells monitored was observed, indicating a general blockade of cellular inflammation. Non-mannosylated phosphatidylinositol (PI) had no suppressive effect, indicating that at least one alpha-d-mannopyranosyl residue is necessary for activity. The suppressive effect of the three PIM compounds indicates that other members of this set may be of value in treatment of a range of diseases driven by infiltration of inflammatory cells.
Ainge
Gary D
GD
Industrial Research Limited, Lower Hutt, New Zealand.
Hudson
Jennifer
J
Larsen
David S
DS
Painter
Gavin F
GF
Gill
Gurmit Singh
GS
Harper
Jacquie L
JL
D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010716:Phosphatidylinositols / Q000138:chemical synthesis / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D018926:Anti-Allergic Agents; D010716:Phosphatidylinositols; C034154:phosphatidylinositol mannoside