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
Sr. Lewin et al., 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, Journal of virology, 71(3), 1997, pp. 2114-2119
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.