Oxidative burst in lipopolysaccharide-activated human alveolar macrophages is inhibited by interleukin-9.
Interleukin (IL)-9 is known to regulate many cell types involved in T-helper type 2 responses classically associated with asthma, including B- and T-lymphocytes, mast cells, eosinophils and epithelial cells. In contrast, target cells mediating the effects of IL-9 in the lower respiratory tract remain to be identified. Therefore, the authors evaluated the activity of IL-9 on human alveolar macrophages (AM) from healthy volunteers. AM preincubated with IL-9 before lipopolysaccharide (LPS) stimulation exhibited a decreased oxidative burst, as previously shown with IL-4. The inhibitory effect of IL-9 was abolished by anti-hIL-9R alpha monoclonal antibody, and presence of IL-9 receptors on AM was demonstrated by immunofluorescence. Both IL-4 and IL-9 failed to modulate tumour necrosis factor-alpha, IL-8 and IL-10 release by LPS-stimulated AM. However, several observations suggested that IL-9 and IL-4 act through different mechanisms: 1) interferon-gamma antagonised the IL4- but not the IL-9-mediated inhibition of AM oxidative burst; 2) expression of CD14 was downregulated by IL-4 but not by IL-9 and 3) production of tumour growth factor-beta by activated AM was potentiated by IL-9 and not by IL4, and was required for the IL-9-mediated inhibition of AM oxidative burst. These observations provide additional information concerning the activity of interleukin-9 in the lung, related to inflammatory or fibrosing lung processes.
Pilette
C
C
Experimental Medicine Unit, Université de Louvain, Brussels, Belgium. charles.pilette@mexp.ucl.ac.be
Ouadrhiri
Y
Y
Van Snick
J
J
Renauld
J C
JC
Staquet
P
P
Vaerman
J P
JP
Sibille
Y
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000276:immunology; D053651:Receptors, Interleukin-9; D016897:Respiratory Burst / Q000187:drug effects
D000911:Antibodies, Monoclonal; D016207:Cytokines; C508045:IL9R protein, human; D016906:Interleukin-9; D008070:Lipopolysaccharides; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9; D015847:Interleukin-4; D007371:Interferon-gamma