EFFECTS OF CHRONIC TREATMENT WITH THE C-KIT LIGAND, STEM-CELL FACTOR,ON IMMUNOGLOBULIN-E DEPENDENT ANAPHYLAXIS IN MICE - GENETICALLY MAST-CELL DEFICIENT SL SL(D) MICE ACQUIRE ANAPHYLACTIC RESPONSIVENESS, BUT THE CONGENIC NORMAL MICE DO NOT EXHIBIT AUGMENTED RESPONSES/

We treated genetically mast cell-deficient WCB6F1-Sl/Sl(d) mice and th e congenic normal (WCB6F1-+/+) mice with the c-kit ligand recombinant rat stem cell factor164 (rrSCF164; 100 mug/kg per d, subcutaneously) o r with vehicle for 21 d, then passively sensitized the mice with anti- dinitrophenol30-40 immunoglobulin E (IgE) antibodies, and 1 d later me asured the changes in heart rate, pulmonary dynamic compliance, and pu lmonary conductance, and assessed the death rates associated with intr avenous challenge of these animals with specific antigen. rrSCF164 tre atment induced the development of mast cells in Sl/Sl(d) mice, and the se mice exhibited tachycardia, but not death, after challenge with IgE and antigen. rrSCF164 treatment induced mast cell hyperplasia in +/mice, but the cardiopulmonary changes associated with passive anaphyla xis in these mice were virtually indistinguishable from those observed in control +/+ mice treated with vehicle instead of rrSCF164. Moreove r, the highest dose of antigen challenge produced significantly fewer fatalities in rrSCF164-treated than in vehicle-treated +/+ mice (1/11 vs. 8/11, respectively, P < 0.01). Thus, in normal mice, chronic treat ment with rrSCF164 induces mast cell hyperplasia but does not increase , and in certain respects diminishes, the severity of IgE-dependent an aphylactic reactions.