PMID- 8300158 OWN - NLM STAT- MEDLINE DCOM- 19940310 LR - 20191023 IS - 0882-0139 (Print) IS - 0882-0139 (Linking) VI - 22 IP - 8 DP - 1993 Dec TI - Nitric oxide mediates the toxoplasmastatic activity of murine microglial cells in vitro. PG - 487-501 AB - Toxoplasma gondii (T. gondii), an opportunistic protozoan, is an important cause of central nervous system (CNS) infections in immunosuppressed patients. The present study focused on the interaction between T. gondii and microglial cells from the brain of neonatal Balb/c mice. Preincubation of the murine microglial cells with recombinant interferon-gamma (rIFN-gamma) and lipopolysaccharide (LPS) induced significant inhibition of T. gondii replication in a dose dependent manner. This antiparasitic effect in microglial cells was correlated with the induction of the L-arginine-dependent generation of reactive nitrogen intermediates (RNIs). Tumor necrosis factor-alpha (TNF-alpha) was also involved in the toxoplasmastatic activity. Microglial cells incubated with recombinant TNF-alpha in combination with a non-activating concentration of rIFN-gamma released substantial amount of RNIs. Neutralizing antibodies against mouse TNF-alpha inhibited the release of RNI by rIFN-gamma activated macrophages. In summary, the present results show that activation of microglial cells by rIFN-gamma and LPS induce the production of nitric oxide (NO) by these cells via an L-arginine dependent pathway. NO appears to be the effector molecule mediating the toxoplasmastatic effects in these cells. FAU - Jun, C D AU - Jun CD AD - Department of Microbiology/Immunology, School of Medicine, Wonkwang University, Korea. FAU - Kim, S H AU - Kim SH FAU - Soh, C T AU - Soh CT FAU - Kang, S S AU - Kang SS FAU - Chung, H T AU - Chung HT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunol Invest JT - Immunological investigations JID - 8504629 RN - 0 (Lipopolysaccharides) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) RN - 94ZLA3W45F (Arginine) SB - IM MH - Animals MH - Arginine/physiology MH - Brain/cytology/*immunology/parasitology MH - Cells, Cultured MH - Fluorescent Antibody Technique MH - Interferon-gamma/pharmacology MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Microglia/*immunology/parasitology MH - Nitric Oxide/*physiology MH - Recombinant Proteins MH - Toxoplasma/*immunology MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1993/12/01 00:00 MHDA- 1993/12/01 00:01 CRDT- 1993/12/01 00:00 PHST- 1993/12/01 00:00 [pubmed] PHST- 1993/12/01 00:01 [medline] PHST- 1993/12/01 00:00 [entrez] AID - 10.3109/08820139309084178 [doi] PST - ppublish SO - Immunol Invest. 1993 Dec;22(8):487-501. doi: 10.3109/08820139309084178.