Effect of cyclic adenosine monophosphate and prostaglandin E2 on multinucleated giant cell formation from human monocytes in sarcoidosis

Abstract

Multinucleated giant cells(MGC) are characteristic cells in granulomatous disorders and derived from monocyte-macrophage lineage cells. The exact mechanisms of MGC formation are not determined. Cyclic adenosine monophosphate(cAMP) is the intracellular second messenger for immunoregulatory mediators and plays a key role in regulation of monocyte-macrophage-mediated inflammatory responses. Here we examined the effects of cAMP on MGC formation. When monocytes were cultured with ConA-stimulated mononuclear cell supernatants(CS), MGC were formed on day 3. MGC formation was significantly suppressed by adding phosphodiesterase inhibitors(PDEI). MGC formation is a complex event involving plasma membrane receptors that are responsible for adhesion, activation and the fusion process. Monocytes cultured with CS highly expressed CD11a and CD54. The addition of PDEI decreased these expressions. Sarcoidosis is a granulomatous disorder with MGC appearance. To investigate the relevance of cAMP in sarcoidosis, we measured serum cAMP level and intracellular cAMP concentration. There was no significant difference in the serum cAMP level between healthy controls(HC) and sarcoidosis patients(SP). On the other hand, there was a significant difference in the intracellular cAMP concentration in monocytes. Because prostaglandin E2(PGE2) affected the cAMP level, we determined the localization of PGE2 in the skin lesion of sarcoidosis. PGE2 was not detectable in the sarcoidal lesion. Furthermore, there was no significant difference in the serum levels of PGE2 of HC and SP. These findings indicate that up-regulation of cAMP in human monocytes inhibited the MGC formation, suggesting that cAMP is a mediator of the granuloma formation. However, PGE2 is not related to this mechanism in sarcoidosis. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF