Cellular responses of guinea-pig macrophages to C4a; inhibition of C3a-induced O2- generation by C4a.
We have investigated the cellular responses of guinea-pig macrophages to human C4a. C4a induced a biphasic Ca2+ mobilization; a rapid temporary Ca2+ mobilization from intracellular Ca2+ pool followed by a weak Ca2+ influx of extracellular Ca2+. Although the C4a-treated macrophages did not respond again to C4a, that is, desensitization to C4a, the C4a-desensitized macrophages still responded to C3a to induce a Ca2+ mobilization. Furthermore, C4a failed to inhibit [125I]-C3a binding to macrophages, suggesting that C4a receptors are different from C3a receptors. In contrast to C3a, C4a-induced Ca2+ mobilization didn't link to O2- generation but inhibited the C3a-induced O2- generation. These results suggest that C4a binds to a specific C4a receptor on guinea-pig macrophages to down-regulate the C3a receptor-mediated O2- generation in macrophages.
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Y
Y
Murakami
T
T
Yamamoto
T
T
Imamichi
S
S
Nagasawa
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015926:Complement C3a / Q000276:immunology*; D015934:Complement C4a / Q000276:immunology*; D015536:Down-Regulation; D016257:Fura-2; D006168:Guinea Pigs; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D011951:Receptors, Complement / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*
D011951:Receptors, Complement; D013481:Superoxides; D015926:Complement C3a; D015934:Complement C4a; D002118:Calcium; D016257:Fura-2