Elsevier

Cytokine

Volume 12, Issue 11, November 2000, Pages 1639-1646
Cytokine

Regular Article
ROLE OF TYPE I INTERFERONS DURING MACROPHAGE ACTIVATION BY LIPOPOLYSACCHARIDE

https://doi.org/10.1006/cyto.2000.0766Get rights and content

Abstract

Activation of macrophages by bacterial lipopolysaccharide (LPS) is accompanied by the secretion of type I interferons (IFNs) which can act in an autocrine manner. We examined the role of type I IFNs in macrophage responses to LPS using bone marrow-derived macrophages (BMM) from IFNAR1-/- mice, which lack a component of the type I IFN receptor and do not respond to type I IFNs. We found that, unlike wild-type (WT) BMM, LPS-treated IFNAR1-/- cells failed to produce nitric oxide (NO), or express inducible NO synthase (iNOS), indicating that type I IFNs are essential for all LPS-stimulated NO production in BMM. Exogenously added type II IFN (IFNγ) rescued these responses in LPS-treated IFNAR1-/- BMM. In contrast to effects on NO, type I IFNs negatively regulated respiratory burst activity in LPS-primed BMM. We also found that while type I IFNs mediated the anti-proliferative effects of lower concentrations of LPS, at higher concentrations LPS acted in a type I IFNs-independent manner. Finally, we report that type I IFNs are a survival factor for BMM. Despite this, the ability of LPS to also prevent apoptosis in BMM was independent of type I IFNs. These findings highlight the diverse roles of type I IFNs in mediating LPS-stimulated macrophage responses.

References (34)

  • LA DiPietro

    Wound healing: the role of the macrophage and other immune cells. [Review] [72 refs]

    Shock

    (1995)
  • SI Hamburg et al.

    Mononuclear phagocytes: responders to and producers of interferon

    Ann N Y Acad Sci

    (1980)
  • F Belardelli et al.

    Studies on the expression of spontaneous and induced interferons in mouse peritoneal macrophages by means of monoclonal antibodies to mouse interferons

    J Gen Virol

    (1987)
  • N Maehara et al.

    Cellular origin of interferon induced by bacterial lipopolysaccharide

    Infect Immun

    (1977)
  • G Uze et al.

    Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background

    Proc Natl Acad Sci USA

    (1992)
  • I Gresser et al.

    Injection of mice with antibody to mouse interferon alpha/beta decreases the level of 2′–5′ oligoadenylate synthetase in peritoneal macrophages

    J Virol

    (1985)
  • SY Hwang et al.

    A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses [published erratum appears in Proc Natl Acad Sci USA 1996 Apr 30;93(9)4519]

    Proc Natl Acad Sci USA

    (1995)
  • Cited by (49)

    • Role of cellular metabolism in regulating type I interferon responses: Implications for tumour immunology and treatment

      2017, Cancer Letters
      Citation Excerpt :

      The selective use of NOS or arginase contributes to the functional polarization of these cells into inflammatory M1 or anti-inflammatory M2 phenotypes, respectively [180–182]. Type I IFN responses, increased expression of inducible NOS is associated with elevated levels of l-citrulline, NO and reactive nitrogen species (Fig. 1) [183,184]. This reprogramming plays and accumulation of these bioactive metabolites plays an important role in mediating cytostatic or cytotoxic activities against viruses, bacteria, fungi, protozoa, helminths and tumour cells [176].

    View all citing articles on Scopus
    f2

    Correspondence to: Dr Peter Vadiveloo, Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital Melbourne, Fitzroy, Australia, 3065. E-mail:[email protected]

    f1

    Current address: ExGenix Operations Pty Ltd, 576 Swan Street, Richmond, Australia, 3121.

    View full text