Effects of chronic treatment with the c-kit ligand, stem cell factor, on immunoglobulin E-dependent anaphylaxis in mice. Genetically mast cell-deficient Sl/Sld mice acquire anaphylactic responsiveness, but the congenic normal mice do not exhibit augmented responses.
We treated genetically mast cell-deficient WCB6F1-Sl/Sld mice and the congenic normal (WCB6F1(-)+/+) mice with the c-kit ligand recombinant rat stem cell factor164 (rrSCF164; 100 micrograms/kg per d, subcutaneously) or with vehicle for 21 d, then passively sensitized the mice with anti-dinitrophenol30-40 immunoglobulin E (IgE) antibodies, and 1 d later measured the changes in heart rate, pulmonary dynamic compliance, and pulmonary conductance, and assessed the death rates associated with intravenous challenge of these animals with specific antigen. rrSCF164 treatment induced the development of mast cells in Sl/Sld mice, and these 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 anaphylaxis in these mice were virtually indistinguishable from those observed in control +/+ mice treated with vehicle instead of rrSCF164. Moreover, 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 treatment with rrSCF164 induces mast cell hyperplasia but does not increase, and in certain respects diminishes, the severity of IgE-dependent anaphylactic reactions.
Ando
A
A
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
Martin
T R
TR
Galli
S J
SJ
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009928:Organ Specificity; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000276:immunology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D012709:Serum Albumin; D019089:Stem Cell Factor; D007073:Immunoglobulin E