Effect of human lung allograft alveolar macrophages on IgG production: immunoregulatory role of interleukin-10, transforming growth factor-beta, and interleukin-6.

D. S. Wilkes, M. Neimeier, P. N. Mathur, D. M. Soliman, Homer Twigg, L. K. Bowen, K. M. Heidler

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Abstract

Alveolar macrophages (AM) are crucial to initiating and maintaining local immune responses. The increased susceptibility to pulmonary infections in lung allograft recipients may be due to impaired AM function resulting in diminished cellular and humoral immunity. We have previously reported that control AM were potent stimulators of IgG production from allogeneic peripheral blood mononuclear cells (PBM) in a manner that was dependent on gamma-interferon (gamma IFN). The ability of allograft AM to induce IgG production is unknown. The purpose of the current study was to compare the ability of allograft and control AM to induce IgG production from allogeneic PBM. In contrast to control AM which induced a dose-dependent stimulation of IgG production from allogeneic PBM, allograft AM were highly suppressive of IgG production. The inhibition was not due to a lack of allograft AM stimulation of gamma IFN production from responding lymphocytes. Supernatants from allograft AM were highly suppressive of control AM-induced IgG production. Allograft AM produced greater quantities of interleukin (IL-10) than control AM while transforming growth factor-beta (TGF-beta) production from these cells was comparable. Blocking antibodies to IL-10 and TGF-beta reversed the inhibition of IgG production to 63% and 60% of control, respectively. In addition, the production of interleukin 6 (IL-6), a macrophage-derived cytokine crucial to the stimulation of IgG synthesis, was deficient in the allograft AM. Addition of IL-6 to allograft AM and allogeneic PBM co-cultures restored IgG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)621-628
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume13
Issue number5
StatePublished - Nov 1995

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Alveolar Macrophages
Transforming Growth Factor beta
Interleukin-10
Allografts
Interleukin-6
Immunoglobulin G
Lung
Blood Cells
Blood
Interferon-gamma
Blocking Antibodies
Lymphocytes
Macrophages
Interleukins
Humoral Immunity
Coculture Techniques
Cellular Immunity
Cell Culture Techniques

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Effect of human lung allograft alveolar macrophages on IgG production : immunoregulatory role of interleukin-10, transforming growth factor-beta, and interleukin-6. / Wilkes, D. S.; Neimeier, M.; Mathur, P. N.; Soliman, D. M.; Twigg, Homer; Bowen, L. K.; Heidler, K. M.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 13, No. 5, 11.1995, p. 621-628.

Research output: Contribution to journalArticle

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abstract = "Alveolar macrophages (AM) are crucial to initiating and maintaining local immune responses. The increased susceptibility to pulmonary infections in lung allograft recipients may be due to impaired AM function resulting in diminished cellular and humoral immunity. We have previously reported that control AM were potent stimulators of IgG production from allogeneic peripheral blood mononuclear cells (PBM) in a manner that was dependent on gamma-interferon (gamma IFN). The ability of allograft AM to induce IgG production is unknown. The purpose of the current study was to compare the ability of allograft and control AM to induce IgG production from allogeneic PBM. In contrast to control AM which induced a dose-dependent stimulation of IgG production from allogeneic PBM, allograft AM were highly suppressive of IgG production. The inhibition was not due to a lack of allograft AM stimulation of gamma IFN production from responding lymphocytes. Supernatants from allograft AM were highly suppressive of control AM-induced IgG production. Allograft AM produced greater quantities of interleukin (IL-10) than control AM while transforming growth factor-beta (TGF-beta) production from these cells was comparable. Blocking antibodies to IL-10 and TGF-beta reversed the inhibition of IgG production to 63{\%} and 60{\%} of control, respectively. In addition, the production of interleukin 6 (IL-6), a macrophage-derived cytokine crucial to the stimulation of IgG synthesis, was deficient in the allograft AM. Addition of IL-6 to allograft AM and allogeneic PBM co-cultures restored IgG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)",
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