Stem cell factor (c-kit ligand) influences eosinophil recruitment and histamine levels in allergic airway inflammation.
The increased reactivity of mast cells during allergic airway inflammation has been linked to several aspects of pulmonary disease. A primary inducer of mast cell differentiation, proliferation, and activation has been identified as c-kit ligand or stem cell factor (SCF). In the present study, we used an established murine model of allergic eosinophilic airway inflammation to examine the role of SCF during an Ag-specific airway response. Initial data demonstrates increased SCF protein production at 8 h postchallenge in both lungs and serum of allergen-challenged, but not vehicle-challenged, mice. The immunolocalization of SCF in Ag-challenged lungs suggested that macrophage populations were the primary source of SCF, while epithelial cell regions also stained positive. Intense immunohistochemical staining of macrophages in bronchoalveolar lavage samples recovered from Ag-sensitized mice indicate that these cells may be a significant source of SCF in the lungs. Alveolar macrophages from the airways of normal mice stimulated with either TNF (0.1-10 ng/ml) or IL-4 (10 ng/ml) produced significant levels of SCF. Furthermore, neutralization studies demonstrated that the inhibition of airway SCF during allergen challenge significantly decreased eosinophil, but not neutrophil, infiltration throughout the response. Furthermore, when mice were treated with anti-SCF Ab, histamine levels were significantly reduced at 8 h postchallenge, the time of significant SCF production. Together, these data indicate that the production of SCF during Ag-induced lung inflammation by alveolar macrophages can play a significant role in the subsequent recruitment of eosinophils, possibly via mast cell activation and degranulation.
Lukacs
N W
NW
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Strieter
R M
RM
Lincoln
P M
PM
Brownell
E
E
Pullen
D M
DM
Schock
H J
HJ
Chensue
S W
SW
Taub
D D
DD
Kunkel
S L
SL
D000818:Animals; D000909:Antibodies, Helminth / Q000494:pharmacology; D000947:Antigens, Helminth / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D006632:Histamine / Q000096:biosynthesis*; D006636:Histamine Release / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012550:Schistosoma mansoni / Q000276:immunology; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D019089:Stem Cell Factor; D006632:Histamine