Alteration of macrophage differentiation into accessory and effector cells from exposure to dimethylnitrosamine (DMN) in vivo

Michael J. Myers, Jeffrey K. Pullen, Lawrence B. Schook

Research output: Contribution to journalArticle

Abstract

DMN exposure modulates cellular immunity through alterations in the maturation and hematopoieses of macrophages. DMN-exposed bone marrow stem cells gave rise to increased colony-forming unit-macrophage (CFU-M) colonies while the resulting colonies produced fewer cells/colony. Bone marrow-derived macrophages phenotypically had decreased cells expressing Ia antigens or cells in the S-phase following DMN treatment. Concanavalin A-elicited peritoneal exudate cells from DMN-treated animals demonstrated an increase in the percentage of macrophages and in the number of immature, bi-nucleated cells obtained as well as a concomitant increase in the percentage of Ia antigen-expressing cells. Concanavalin A-elicited peritoneal exudate cells from DMN-exposed animals also had an increased secreted interleukin-1 activity following lipopolysaccharide stimulation without any alteration in the expression of membrane-bound interleukin-1. Thioglycolate-elicited peritoneal exudate cells from DMN-exposed animals demonstrated no changes in cellularity and only showed increases in the percentage of bi-nucleated cells. There were no alterations in the capacity of T cells obtained from DMN-treated animals to respond to either soluble (keyhole limpet hemocyanin) or allo-antigens; nor were there alterations in the capacity of these T cells to either produce or respond to interleukin-2. These findings suggest that the observed DMN-induced modulation(s) in cell-mediated immunity results from changes in macrophage hematopoieses due to alterations in: (1) the production of regulatory factors controlling their production and/or differentiation or (2) their ability to respond to these factors.

Original languageEnglish (US)
Pages (from-to)105-115
Number of pages11
JournalImmunopharmacology
Volume12
Issue number2
DOIs
StatePublished - Oct 1986
Externally publishedYes

Keywords

  • Bone marrow-derived macrophage
  • Dimethylnitrosamine
  • Macrophage heterogeneity

ASJC Scopus subject areas

  • Pharmacology

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