A suppressive role of nitric oxide in MIP-2 production by macrophages upon coculturing with apoptotic cells.
Macrophages phagocytose apoptotic cells without causing neutrophil infiltration in vivo under physiological conditions. Our recent study, however, showed that macrophages produce IL-8 or MIP-2, a murine IL-8 homologue, upon coculturing with apoptotic cells, indicating that there must be unknown mechanisms for preventing IL-8 or MIP-2 production. As activated macrophages produce NO to regulate inflammation, we examined the NO production by macrophages upon coculturing with apoptotic or necrotic cells and explored the role of NO in MIP-2 production. NO was produced on coculturing with early apoptotic cells much more significantly than with late apoptotic or necrotic cells. On the contrary, MIP-2 was produced on coculturing with late apoptotic or necrotic cells much more significantly than with early apoptotic cells. N(G)-Nitro-L-arginine methyl ester, an inhibitor of NO synthase, or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of NO, augmented MIP-2 production on coculturing with early apoptotic cells. The addition of N-ethylethanamine:1,1-diethyl-2-hydroxy-2-nitrosohydrazine [1:1], a donor of NO, conversely, caused suppression of MIP-2 production on coculturing with late apoptotic cells. These results suggest an important role of NO for preventing MIP-2 production by macrophages upon coculturing with early apoptotic cells.
Shibata
Takehiko
T
Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba 274-8510, Japan.
Nagata
Kisaburo
K
Kobayashi
Yoshiro
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D054426:Chemokine CXCL2; D018920:Coculture Techniques / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D015846:Monokines / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D013329:Structure-Activity Relationship
D054426:Chemokine CXCL2; D015846:Monokines; D016328:NF-kappa B; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases