title: Evidence for endogenous C1q modulates TNF-alpha receptor synthesis and autocrine binding of TNF-alpha associated with lipid A activation of murine macrophages for nitric oxide production.
abstract: The role of endogenously synthesized complement subcomponent C1q on autocrine binding of tumor necrosis factors (TNF-alpha) and on TNF-alpha receptor (TNF-R) mRNA synthesis by mouse macrophages was investigated. Activation of C3H mouse peritoneal macrophages (C3H-PM phi) by Lipid A induced TNF-alpha and nitric oxide (NO) to kill tumor targets. Such activation also increased macrophage-endogenous C1q synthesis and secretion in a dose-dependent fashion. Antibody for C1q markedly inhibited C3H-PM phi NO production in response to Lipid A, but had no effect on TNF-alpha production. C3H-PM phi treated with C1q or Lipid A displayed increased TNF-R mRNA synthesis and in combination with Lipid A and anti-C1q antibody inhibited TNF-R and nitric oxide synthase (NOS) mRNA synthesis compared with Lipid A only, but had no effect on TNF mRNA synthesis. In vitro treatment of C3H-PM phi with C1q also increased TNF-alpha binding to their surfaces. Taken together, the data indicate that endogenously synthesized C1q is operative in promoting TNF-R mRNA synthesis and resultant autocrine binding of TNF-alpha for induction of NOS in the process of NO-mediated tumor cytotoxicity by Lipid A-activated macrophages.
authors.affiliation: Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104-5046, USA.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: J A
authors.initials: JA
authors.lastname: Rummage
authors.forename: C A
authors.initials: CA
authors.lastname: Stewart
authors.forename: M J
authors.initials: MJ
authors.lastname: Herriott
authors.forename: I
authors.initials: I
authors.lastname: Kolosova
authors.forename: M
authors.initials: M
authors.lastname: Kolosov
authors.forename: R W
authors.initials: RW
authors.lastname: Leu
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D015922:Complement C1q / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008050:Lipid A / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D008050:Lipid A; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015922:Complement C1q; D019001:Nitric Oxide Synthase