Modulation of HIV-1 expression in monocyte derived macrophages by substance P.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Modulation of HIV-1 expression in monocyte derived macrophages by substance P.

Abstr Gen Meet Am Soc Microbiol. 1994;94:622 (abstract no. V-31). Unique Identifier : AIDSLINE ASM94/94313121
Ho WZ; Douglas SD; Children's Hospital of Philadelphia, PA.

Abstract: The monocyte-macrophage system is a valuable in vitro model to investigate the pathogenesis of HIV-1 infection and AIDS dementia. Substance P (SP) modulates a number of important immunological functions of monocyte-macrophages. We have studied the effects of SP on HIV-1 p24 antigen expression and reverse transcriptase (RT) activity in primary cultures of monocyte derived macrophages (MDM). The addition of SP at concentrations of 10(-10) to 10(-6) M results in enhanced HIV-1 replication in MDM in a concentration-dependent manner, with the optimal effect observed on day 8-12. MDM were studied from 13 healthy donors; 7 of these donors' cells treated with 10(-8) M of SP showed a 2 to 8-fold increase in both p24 antigen expression and RT measured 4, 8, 12 and 16 days following HIV-1 (Bal) infection. Furthermore, SP, when added to HIV-1 infected MDM cultures, reverses lipopolysaccharide (LPS) induced inhibition of HIV-1 replication in a dose dependent manner. SP enhances HIV-1 expression in an SP receptor bearing cell line (Jurkat-SPR) in comparison with the same line which does not express SP receptors (Jurkat-Vector). SP stimulated TNF production in 14-day-cultured MDM as determined by a L929 cytotoxicity assay, suggesting that induced TNF may be related to SP enhanced HIV-1 replication in MDM. These effects of SP may have in vivo implications which are relevant to HIV-1 infection of monocytes-macrophages, to the modulation of monocyte-macrophage functions and to the immunopathogenesis of HIV-1 infection in the brain.

Keywords: Cell Line Cells, Cultured Comparative Study Human HIV Core Protein p24/BIOSYNTHESIS HIV-1/DRUG EFFECTS/*PHYSIOLOGY Macrophages/DRUG EFFECTS/*MICROBIOLOGY/*PHYSIOLOGY Monocytes/CYTOLOGY/*PHYSIOLOGY Receptors, Neurokinin-1/METABOLISM Reference Values RNA-Directed DNA Polymerase/BIOSYNTHESIS Substance P/*PHARMACOLOGY Time Factors Virus Replication/*DRUG EFFECTS ABSTRACT
941030
M94A0833

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