Inhibition ofthereactive proliferation oflymphocytes by activated macrophages: theroleofnitric oxide

SUMMARY Theeffectsofnitricoxidesynthesisbyactivatedmacrophages on concanavalinA(ConA)stimulatedlymphocyteproliferationandthemodulationoftheseeventsbyextraneousL-arginineconcentration were investigated. In 1 mm or 5 mm exogenous L-arginine, inhibition ofproliferation of a fixednumber of lymphocytes was progressively inhibited in the presence of increasing numbers ofmacrophages. Thisinhibition was related to increasednitricoxidesynthesisbythemacrophagesand was suppressedin the presence ofNG-monomethyl-L-arginine(NMMA), a specificinhibitorofnitricoxide synthesis. Inhibition ofnitric oxide synthesis by 500 gm NMMA was less effective at highconcentrations of macrophages, andin 5 mm as comparedwith 1 mM L-arginine. In the absenceof exogenous L-arginine, NMMAinhibitedlymphocyteproliferationinthe presence oflownumbersofmacrophagesbutappeared topromote proliferation at highmacrophageconcentrations. Membraneseparationoflymphocytesandmacrophagesled to lossofthenitric oxidemediatedinhibitoryeffect