A critical role for alveolar macrophages in elicitation of pulmonary immune fibrosis.
Hapten immune pulmonary interstitial fibrosis (HIPIF) is induced by a recall cell-mediated immune response against the hapten 2,4, 6-trinitrobenzene sulphonic acid (TNBS) in the lung. Studies here dissect the role of the cellular components of the bronchoalveolar lavage (BAL) cells (alveolar macrophages [AMs] versus monocytes and immature dendritic cells) in the fibrogenic inflammatory response. BAL cells from HIPIF mice were generally more activated and produced a greater amount of tumour necrosis factor-alpha (TNF-alpha) than controls. Liposome-encapsulated dichloromethylene diphosphonate (Cl(2)MDP) that was inoculated intranasally (i.n.) into mice selectively depleted AMs. Following AM depletion, the number of TNF-alpha-containing cells was reduced, and both the number of immune inflammatory cells recruited into the alveolar space and the subsequent collagen deposition (hydroxyproline) were decreased in the sensitized and intratracheally (i.t.) challenged mice. In conclusion, AMs are required, in part, for the development of pulmonary fibrosis in HIPIF because AM-derived factors such as TNF-alpha are needed for initiation of chemokine and cytokine pathways and accumulation of immune inflammatory cells.
Zhang-Hoover
J
J
Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
Sutton
A
A
van Rooijen
N
N
Stein-Streilein
J
J
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology; D006909:Hydroxyproline / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D006241:Haptens; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D006909:Hydroxyproline