Stem cell factor-induced airway hyperreactivity in allergic and normal mice.
The induction of airway hyperreactivity during allergic responses involves multiple ill-defined mechanisms. Recently a role for stem cell factor (SCF) in the development of allergic eosinophilic airway inflammation has been identified. In the present study we demonstrate that SCF has a role in both the inflammatory response and airway hyperreactivity. Neutralization of SCF or examination of SCF-mutant mice, which were deficient in SCF and pulmonary mast cells, demonstrated significant alterations in the allergen-induced airway hyperreactive responses. The reduced hyperreactivity response was accompanied by a significant reduction in eosinophil accumulation. To examine the direct role of SCF on airway hyperreactivity, we administered SCF into the airways of normal mice via intratracheal injections and demonstrated a dose dependent increase in airway hyperreactivity at 4 hours that was maintained at 24 hours after administration. Instillation of SCF into SCF-deficient (mast cell deficient) mice demonstrated significantly lower increases in airway hyperreactivity compared with the littermate controls with normal mast cell numbers. These studies demonstrate that locally expressed SCF can induce changes in airway physiology via mast cell activation, verifying the role of SCF in allergic airway inflammation and hyperreactivity.
Campbell
E
E
University of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan 48109-0602, USA.
Hogaboam
C
C
Lincoln
P
P
Lukacs
N W
NW
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D007074:Immunoglobulin G / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology*; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000276:immunology*
D000947:Antigens, Helminth; D007074:Immunoglobulin G; D019089:Stem Cell Factor; D016210:Methacholine Chloride