Inhibition of macrophage phagocytosis by methylation inhibitors. Lack of correlation of protein carboxymethylation and phospholipid methylation with phagocytosis.

摘要: Adenosine (Ado), deoxyadenosine (dAdo), and adenine arabinoside (AraA) inhibit the phagocytosis of IgG-coated erythrocytes zymosan by resident thioglycollate-elicited macrophages (thio-macrophages) in a dose-dependent reversible manner. 3-Deazaadenosine (3cAdo) (Ade) also macrophages. Homocysteine thiolactonate (Hcy) potentiates inhibition Ado 3cAdo while erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) Ado, dAdo AraA. This has very rapid onset drugs do not interfere with binding to The combination Hcy EHNA does appreciably affect intracellular level ATP S-adenosyl-L-methionine (AdoMet) thio-macrophages but causes accumulations S-adenosyl-L-homocysteine (AdoHcy) up 135 145 nmol/mg protein, respectively. During reversal, is metabolized within 15 min AdoHcy decreases log-arithmically half-life 50 min. Carboxymethylation phospholipid methylation, however, resume about 60-90 after recovered, thus cannot function as transmembrane signals for phagocytosis. Other evidence showing lack correlation between carboxymethylation include 1) + much better than (91 versus 75%) thio-macrophage, two combinations show comparable potency; 2) almost well EHNA, latter more effective drug inhibition; 3) Ade 3cAdo, although inhibiting macrophage Hcy, are weaker inhibitors; 4) AraA potently carboxymethylation. difference apparent methylation levels due changes specific activities AdoMet, which decrease 88 Interestingly, initial lag phase 90 initiation increase parallel. In log-log plot carboxymethylation, or accumulation, linear relationship obtained. It possible that accumulation responsible inhibits mechanism other interfering protein lipid methylations.