Effects of concanavalin A and Fc fragments of IgG on human monocyte cAMP content: modulation of monocyte secretory function by cAMP.

Exposure of human monocytes in monolayer culture to concanavalin A (Con A) or Fc fragments of IgG results in decreased levels of lysozyme, acid phosphatase and the second component of complement (C2), but increased levels of prostaglandin E (PGE) in the culture medium. Indomethacin blocked the effect of Con A and Fc fragments on PGE levels but did not alter the effects on the other secretory products. The addition of Con A to the monocyte cultures resulted in increased cAMP levels in short (<20 min) and in long term incubations (24 hr). Long term exposure to the Fc fragments of IgG also resulted in elevated levels of cAMP. In long term cultures, elevation of cAMP levels by Fc fragments and Con A may in part be mediated by stimulation of endogenous prostaglandin production, since addition of indomethacin resulted in a return of cAMP towards basal levels. The addition of D-L isoproterenol, IBMX, or exogenous PGE, reagents that increase cAMP content, or addition of Dibutyryl 3′, 5′ adenosine monophosphate (DBcAMP) to cultures resulted in a dose-dependent inhibition of secretion of acid phosphatase, lysozyme and C2. These findings suggest that certain secretory responses of human monocytes are reduced by agents which increase cAMP levels. These changes may be related to direct effects on adenylate cyclase stimulation or indirect effects on the release of other products which effect cAMP generation. These changes in cAMP content may in part be responsible for the reduced secretory response.