Allergen-induced increase in bone marrow progenitors in airway hyperresponsive dogs: regulation by a serum hemopoietic factor.
We have previously reported that bone marrow progenitors in dogs, specifically granulocyte-macrophage colony-forming units (GM-CFU), increase developing airway hyperresponsiveness after inhalation of the allergen Ascaris suum. In the present study, we evaluated whether this increased marrow hemopoietic activity can be stimulated by a factor in serum after allergen challenge. Serum samples taken from dogs prior to and 20 min, 2 h, and 24 h after Ascaris or diluent challenge were added to bone marrow cells aspirated prior to challenge, and GM-CFU measured. A second bone marrow aspirate was performed 24 h after challenge. Nonadherent mononuclear bone marrow cells were incubated for 8 days in the presence of the serum and recombinant canine hemopoietic cytokines (stem cell factor, granulocyte colony-stimulating factor, GM colony-stimulating factor). Eight dogs that developed (airway responders) and eight dogs that did not develop (airway nonresponders) allergen-induced airway hyperresponsiveness were studied. Allergen inhalation increased bone marrow GM-CFU in response to all three growth media in vitro for the airway responder (P < 0.05) but not airway nonresponder dogs. The 24-h serum, taken from the airway responder but not the airway nonresponder dogs, produced a similar increase in granulocyte progenitors when added to the bone marrow taken before allergen inhalation (P < 0.05). These findings demonstrate that bone marrow-derived granulocyte progenitors are upregulated by a factor that can be shown to be present in serum 24 h after allergen challenge in dogs that develop allergen-induced airway hyperresponsiveness. Whether in vivo stimulation of bone marrow inflammatory cell production is necessary for the development of allergen-induced airway hyperresponsiveness remains to be proven.
Inman
M D
MD
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Denburg
J A
JA
Ellis
R
R
Dahlback
M
M
O'Byrne
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000485:Allergens / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D017165:Ascaris suum / Q000276:immunology; D001854:Bone Marrow Cells; D016535:Bronchial Hyperreactivity / Q000097:blood* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D003114:Colony-Forming Units Assay; D004285:Dogs; D016298:Hematopoietic Cell Growth Factors / Q000097:blood / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D000485:Allergens; D016298:Hematopoietic Cell Growth Factors; D000109:Acetylcholine