Targeted Fc2'-3-PE40 chimeric protein abolishes passive cutaneous anaphylaxis in mice.
The alarming increase in the incidence of allergic diseases in the past decade has led to a clear call for more effective treatment. Recently, we reported on the construction of a chimeric protein for targeted elimination of cells expressing FcepsilonRI receptors. This chimeric protein, designated Fc2'-3-PE40, is composed of a Fc fragment of mouse IgE attached to a truncated form of Pseudomonas exotoxin. The Fc2'-3-PE40 chimeric protein was found to be highly cytotoxic to mouse mast cell lines and primary mouse mast cells. We now demonstrate that Fc2'-3-PE40 successfully prevents the development of passive cutaneous anaphylaxis reaction (PCA) in mice. Treatment with Fc2'-3-PE40 for 7 days prevented the PCA reaction in mice by 80% compared with that in control mice given only PBS. Fc2'-3-PE40M, the mutated, enzymatically inactive analogue of Fc2'-3-PE40, did not display this activity. Fc2'-3-PE40 was also effective when given as a single dose 16 h before antigen exposure, resulting in complete inhibition of the PCA reaction. Moreover, treatment with Fc2'-3-PE40 did not cause mast cell degranulation, as the serum histamine values of mice treated with Fc2'-3-PE40 were within the range obtained for control, untreated mice. Thus, the Fc2'-3-PE40 chimeric protein offers a novel approach to the treatment of allergic disorders.
Fishman
A
A
Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Prus
D
D
Belostotsky
R
R
Lorberboum-Galski
H
H
D000707:Anaphylaxis / Q000276:immunology* / Q000628:therapy*; D000818:Animals; D005098:Exotoxins / Q000276:immunology* / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D011549:Pseudomonas; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D012867:Skin / Q000276:immunology / Q000473:pathology
D005098:Exotoxins; D007141:Immunoglobulin Fc Fragments; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins