Inhibition of chemotaxis by S-3-deazaadenosylhomocysteine in a mouse macrophage cell line.
Chemotaxis by a macrophage cell line, RAW264, is specifically inhibited by the intracellular accumulation of 3-deazaadenosylhomocysteine (3-deaza-AdoHcy). Intracellular accumulation of 3-deaza-AdoHcy is the result of incubation of the cells with 3-deazaadenosine, a compound that can function both as a substrate and as an inhibitor of adenosylhomocysteine (AdoHcy) hydrolase. Accumulation of AdoHcy per se, brought about in chemotactic cell lines by incubation with either 3-deazaadenosine or with 3-deazaaristeromycin, does not affect chemotaxis. The specific role of 3-deazaadenosine as an inhibitor of macrophage cell line chemotaxis is supported by the following findings. Another macrophage cell line, RAW309CR, is resistant to the inhibition of chemotaxis by 3-deazaadenosine, and the resistance can be ascribed to the failure to accumulate 3-deaza-AdoHcy in this cell line. It is noteworthy that both RAW264 and RAW309CR accumulate similar amounts of AdoHcy after incubation with 3-deazaadenosine. The difference in the accumulation of 3-deaza-AdoHcy in RAW264 and RAW309CR is explained by the finding that sonicates of RAW264 rapidly form 3-deaza-AdoHcy but sonicates of RAW309CR do not. Both hydrolysis of AdoHcy and the inhibition of the hydrolysis of AdoHcy by 3-deazaadenosine are the same in sonicates of the two macrophage cell lines.
D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D006710:Homocysteine / Q000031:analogs & derivatives*; D007536:Isomerism; D007700:Kinetics; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014372:Tubercidin / Q000494:pharmacology
C018258:3-deazaadenosine; D006710:Homocysteine; C033256:S-(3-deazaadenosyl)homocysteine; D012435:S-Adenosylhomocysteine; D014372:Tubercidin