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M9480824.TXT
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1994-09-05
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).