AEGiS-14IAC: HIV enhances substance P expression in human immune cells.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

HIV enhances substance P expression in human immune cells.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. A10018)

Li Y, Ho WZ, Lai JP, Douglas SD
Children's Hospital of pHiladelphia, Philadelphia, United States

BACKGROUND: Substance P (SP), the most potent member of tachykinin family, is a modulator of neuroimmunoregulation. We have demonstrated that human immune cells express SP and its receptor. In in vitro studies, it has been documented that SP is involved in the immunopathogenesis of HIV infection. We have recently observed that increased levels of plasma SP in HIV-infected men than uninfected control subjects. However, the cellular source of the elevated levels of plasma SP has not yet been defined.

METHODS: Real-time reverse transcribed polymerase chain reaction (RT-PCR) was utilized to quantitate SP mRNA and enzyme immunoassay was used to measure SP peptide present in culture supernatants. HIV RT activity was determined by RT assay.

RESULTS: We demonstrated monocyte-derived macrophages (MDM) and lymphocutes from both placental cord blood and adult peripheral blood express SP mRNA, which was significantly increased by HIV infection. HIV-induced SP expression was positively related to the virus replication in the infected MDM. Purified recombinant HIV envelope glycoprotein 120 (gp120) derived from both macrophage-tropic strain (MN) and T lymphocyte-tropic strain (IIIB), when added to MDM cultures, enhanced SP mRNA expression. Gp120-induced SP expression was abrogated by pre-treating the cells with soluble CD4. Furthermore, the activation of HIV in the latently infected promonocytic cell line (U1) and T cell line (ACH-2) up-regulated SP mRNA expression.

CONCLUSION: These data support the hypothesis that interaction of HIV and SP may have significant in vivo relevance to the immunopathogenesis of HIV infection and AIDS.

Keywords: AEGIS, HIV, HIV Infections, Substance P, Virus Replication, Macrophages, HIV Seropositivity, Tachykinins, HIV Long Terminal Repeat, HIV Envelope Protein gp120, T-Lymphocytes, Anti-HIV Agents, HIV Core Protein p24, Cell Line, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Acquired Immunodeficiency Syndrome, Human, Male, Adult, In Vitro, virology, genetics, immunology

020707
A10018