Inhibition of stem cell factor reduces pulmonary cytokine levels during allergic airway responses.
Stem cell factor (SCF) has a significant role in the inflammation and activation of allergic airway responses. When monoclonal anti-SCF was administered intratracheally during allergen challenge there was a significant alteration of eosinophil accumulation and airway hyperreactivity (AHR). Anti-SCF treatment also attenuated pulmonary cytokine and chemokine levels. In particular, there was an antibody dose-dependent decrease in interleukin (IL)-5 and tumour necrosis factor (TNF)-alpha. There was also a significant reduction of CCL2 and CCL5, which correlated with the reduction in AHR. Mice treated with anti-SCF demonstrated a significant decrease in pulmonary gob-5 gene expression, which has been shown to correlate to goblet cell hyperplasia/metaplasia relating to airway mucus production. Blocking SCF-mediated activation within the airway using a monoclonal antibody indicates that this cytokine may represent a viable target for therapeutic intervention that could affect multiple aspects of allergen-induced immunopathology.
Berlin
A A
AA
University of Michigan Medical School, Department of Pathology, Ann Arbor, MI, USA.
Lincoln
P
P
Tomkinson
A
A
Lukacs
N W
NW
D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018925:Chemokines / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004802:Eosinophilia / Q000517:prevention & control; D008168:Lung / Q000276:immunology*; D016210:Methacholine Chloride; D051379:Mice; D008808:Mice, Inbred CBA; D009088:Mucoproteins / Q000378:metabolism; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors* / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D018925:Chemokines; D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D016207:Cytokines; D009088:Mucoproteins; D019089:Stem Cell Factor; D016210:Methacholine Chloride