Document 0824
 DOCN  M9480824
 TI    Modulation of HIV-1 expression in monocyte derived macrophages by
       substance P.
 DT    9410
 AU    Ho WZ; Douglas SD; Children's Hospital of Philadelphia, PA.
 SO    Abstr Gen Meet Am Soc Microbiol. 1994;94:622 (abstract no. V-31). Unique
       Identifier : AIDSLINE ASM94/94313121
 AB    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.
 DE    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  Reverse
       Transcriptase/BIOSYNTHESIS  Substance P/*PHARMACOLOGY  Time Factors
       Virus Replication/*DRUG EFFECTS  MEETING ABSTRACT

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