Markers of macrophage differentiation in experimental silicosis.
Macrophages are characterized by a marked phenotypic heterogeneity depending on their microenvironmental stimulation. Beside classical activation (M1), it has been shown that macrophages could follow a different activation pathway after stimulation with interleukin (IL)-4 or IL-13 (M2). Recently, it has been postulated that those "alternatively activated" macrophages may be critical in the control of fibrogenesis. In an experimental model of silicosis, where pulmonary macrophages play a central role, we addressed the question of whether lung fibrosis development would be associated with alternative macrophage activation. As available markers for alternative macrophage activation, type-1 arginase (Arg-1), Fizz1, Ym1/2, and mannose receptor expression were evaluated at the mRNA and/or protein levels at different stages of the disease. Nitric oxide synthase-2 (NOS-2) expression was also examined to investigate the classical counterpart. We found that the expression of Arg-1, Fizz1, and NOS-2 in adherent bronchoalveolar lavage cells was highly up-regulated 3 days after silica administration but returned to control levels during the fibrotic stage of the disease (60 days). By comparing the early response to silica in C57BL/6 and BALB/c mice, we observed that the amplitude of Arg-1 mRNA up-regulation was not associated with the severity of lung fibrosis. Using a model of manganese dioxide particles (resolutive alveolitis), we showed that this early Arg-1 mRNA was not specific to a fibrogenic lung response. Our data indicate that the modifications of M1/M2 marker expression are limited to the early inflammatory stage of silicosis and that the establishment of a fibrotic process is not necessarily associated with M2 polarization.
Industrial Toxicology and Occupational Medicine, Université Catholique de Louvain, Belgium. pierre-damien.misson@toxi.ucl.ac.be
Pierre
P
Misson
Sybille
S
van den Brûle
Virginie
V
Barbarin
Dominique
D
Lison
François
F
Huaux
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology*; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017895:Manganese Compounds; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010087:Oxides; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012822:Silicon Dioxide; D012829:Silicosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
D000943:Antigens, Differentiation; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D037102:Lectins; D037181:Lectins, C-Type; D017895:Manganese Compounds; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D010087:Oxides; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C413576:Retnla protein, mouse; D015847:Interleukin-4; D012822:Silicon Dioxide; D020932:Nerve Growth Factor; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases; D001119:Arginase; C016552:manganese dioxide