title: Anti-asialo GM1 NK cell depleting antibody does not alter the development of bleomycin induced pulmonary fibrosis.
abstract: Despite circumstantial evidence postulating a protective role for NK cells in many fibrotic conditions, their contribution to the development of pulmonary fibrosis has yet to be tested. Lung-migrating NK cells are thought to attenuate the development of bleomycin induced pulmonary fibrosis (BIPF) by providing anti-fibrotic mediators and cytokines, such as IFN-γ. If true, we reasoned that depletion of NK cells during experimentally-induced fibrotic disease would lead to exacerbated fibrosis. To test this, we treated mice with NK cell-depleting antisera (anti-asialo GM1) and evaluated lung inflammation and fibrosis in the BIPF model. While NK cell infiltration into the airways was maximal at day 10 after bleomycin injection, NK cells represented a minor portion (1-3%) of the total leukocytes in BAL fluid. Anti-asialo GM1 significantly abrogated NK cell numbers over the course of the disease. Depletion of NK cells with anti-asialo GM1 before and throughout the BIPF model, or during just the fibrotic phase did not alter fibrosis development or affect the levels of any of the pro-inflammatory/pro-fibrotic cytokines measured (IL-1β, IL-17, IFN-γ, TGF-β and TNF-α). In addition, adoptively transferred NK cells, which were detectable systemically and in the airways throughout BIPF, failed to impact lung fibrosis. These findings indicate that NK cells likely do not play an essential protective role in controlling pulmonary fibrosis development.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America; Palo Alto Institute for Research and Education, Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Monnier
authors.affiliation: Palo Alto Institute for Research and Education, Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Zabel
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008212:Lymphocyte Depletion; D008807:Mice, Inbred BALB C; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D013154:Spleen / Q000473:pathology
chemical_list: D000906:Antibodies; D016207:Cytokines; D001761:Bleomycin; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside