Expression and regulation of human alveolar macrophage-derived interleukin-1 receptor antagonist.
The alveolar macrophage (AM) is the sentinel immune cell of the distal airspace of the lung. These mononuclear phagocytic cells represent the major host defense against inhaled environmental agents. When activated, the AM has the capacity to release reactive oxygen and arachidonic acid metabolites and produce a number of cytokines, such as interleukin-1 (IL-1). This latter cytokine has pleiotropic effects on a variety of cells and has been implicated as one of the preeminent mediators of acute inflammation. Recently, an IL-1 receptor antagonist (IRAP) has been isolated, purified, and cloned from peripheral blood monocytes (PBM) stimulated with either adherent IgG (adhIgG) lipopolysaccharide (LPS), or phorbol myristate acetate. IRAP acts as a true receptor antagonist without agonist activity. We postulated that the AM would be a significant cellular source of IRAP from the lung. To test this hypothesis, normal human AM were immediately isolated or stimulated in a dose-dependent fashion with either LPS or adhIgG. For comparison, PBM were also isolated and treated in a similar manner. PBM expressed steady-state IRAP mRNA by Northern blot analysis only in response to LPS or adhIgG. In contrast, AM were found to express significant levels of antigenic IRAP by Western blot analysis, immunostaining, and specific ELISA, and express steady-state levels of IRAP mRNA under unstimulated culture conditions. Moreover, LPS or adhIgG failed to induce AM-derived IRAP antigen generation over unstimulated control.(ABSTRACT TRUNCATED AT 250 WORDS)
Moore
S A
SA
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Strieter
R M
RM
Rolfe
M W
MW
Standiford
T J
TJ
Burdick
M D
MD
Kunkel
S L
SL
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012795:Sialoglycoproteins; D013755:Tetradecanoylphorbol Acetate
C507763:IL1RN protein, human; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate