ALLERGEN-INDUCED INCREASE IN BONE-MARROW PROGENITORS IN AIRWAY HYPERRESPONSIVE DOGS - REGULATION BY A SERUM HEMATOPOIETIC FACTOR

We have previously reported that bone marrow progenitors in dogs, spec ifically granulocyte-macrophage colony-forming units (GM-CFU), increas e developing airway hyperresponsiveness after inhalation of the allerg en Ascaris suum. In the present study, we evaluated whether this incre ased marrow hemopoietic activity can be stimulated by a factor in seru m 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 t o bone marrow cells aspirated prior to challenge, and GM-CFU measured. A second bone marrow aspirate was performed 24 h after challenge. Non adherent mononuclear bone marrow cells were incubated for 8 days in th e presence of the serum and recombinant canine hemopoietic cytokines ( stem cell factor, granulocyte colony-stimulating factor, GM colony-sti mulating factor). Eight dogs that developed (airway responders) and ei ght 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 nonres ponder dogs, produced a similar increase in granulocyte progenitors wh en added to the bone marrow taken before allergen inhalation (P < 0.05 ). These findings demonstrate that bone marrow-derived granulocyte pro genitors are upregulated by a factor that can be shown to be present i n serum 24 h after allergen challenge in dogs that develop allergen-in duced airway hyperresponsiveness. Whether in vivo stimulation of bone marrow inflammatory cell production is necessary for the development o f allergen-induced airway hyperresponsiveness remains to be proven.