Recombinant soluble form of the human high-affinity receptor for IgE prevents anaphylactic shock in mice.
The ectodomain of the alpha subunit of the human high-affinity receptor for IgE (Fc epsilon RI) has been engineered as a recombinant soluble protein (sFc epsilon RI alpha) and purified in large quantity from the supernatant of transfected mammalian cells. The sFc epsilon RI alpha was apparently heterogeneous in terms of molecular weight (40 to 60 kd), and this heterogeneity was largely due to N-linked carbohydrates on the molecule. The amino terminal sequence was homogeneous and identical to the sequence predicted from the complementary DNA sequence. The amino acid composition of the sFc epsilon RI alpha was in agreement with the values expected from the cDNA sequence. The sFc epsilon RI alpha formed a complex with IgE, and gel filtration analyses of the complex of the sFc epsilon RI alpha and human IgE supported the idea that the stoichiometry of the IgE binding was 1:1. Passive anaphylactic shock in mice was suppressed when the sFc epsilon RI alpha was intravenously injected after sensitization with anti-trinitrophenyl IgE and challenged with the appropriate antigen. In this model the sFc epsilon RI alpha was effective when administered 48 hours before the antigen challenge, but not 24 hours before the challenge. These results suggest that the sFc epsilon RI alpha facilitated the dissociation of IgE from Fc epsilon RI on mast cells in vivo and suppressed type I allergic reactions.
Naito
K
K
Research Division, Green Cross Corporation, Osaka, Japan.
Hirama
M
M
Okumura
K
K
Ra
C
C
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012995:Solubility; D014162:Transfection
D000596:Amino Acids; D007166:Immunosuppressive Agents; D017455:Receptors, IgE; D011994:Recombinant Proteins; D007073:Immunoglobulin E