CONSTITUTIVE EXPRESSION OF P50 HOMODIMER IN FRESHLY ISOLATED HUMAN MONOCYTES DECREASES IN-VITRO AND IN-VIVO DIFFERENTIATION - A POSSIBLE MECHANISM INFLUENCING HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN MONOCYTES AND MATURE MACROPHAGES

Human immunodeficiency virus type 1 (HIV-1) replicates more efficientl y in vitro in differentiated macrophages than in freshly isolated mono cytes. We investigated whether this may be partly explained by changes in expression of NF-kappa B with monocyte differentiation. We demonst rated that constitutive expression of NF-kappa B in primary human mono cytes changed significantly with differentiation in vitro to monocyte- derived macrophages (MDMs) and differentiation in vivo to alveolar mac rophages (AMs). Freshly isolated monocytes constitutively expressed hi gh levels of transcriptionally inactive p50 homodimer which decreased with time in culture in favor of the transcriptionally active p50/p65 and p50/RelB heterodimers. As in MDMs, AMs constitutively expressed p5 0/p65 and p50/RelB although at lower levels. HIV infection of fresh mo nocytes failed to induce p50/p65 as seen in MDMs. The replacement of p 50 homodimers with transcriptionally active heterodimers following tim e in culture may partially explain the progressive increase in suscept ibility of monocytes to HIV infection during in vitro culture. The cha nge in NF-kappa B components with monocyte differentiation in vivo may also explain the different transcriptional activities of these cell p opulations in HIV-infected individuals.