Conservation of signal transduction mechanisms via the human Fc epsilon RI alpha after transfection into a rat mast cell line, RBL 2H3.
The high affinity receptor for IgE (Fc epsilon RI) is present on mast cells and basophils, and the aggregation of IgE-occupied receptors by Ag is responsible for the release of allergic mediators. The Fc epsilon RI is composed of at least three different subunits, alpha, beta, and gamma, with the alpha subunit binding IgE. The series of biochemical events linking receptor aggregation to the release of mediators has not been fully delineated. As a step towards understanding these processes, and for the development of functional cell lines, we have transfected the human Fc epsilon RI alpha subunit into the rat mast cell line RBL 2H3. These human Fc epsilon RI alpha-transfected cell lines have been characterized with respect to the association of the human alpha subunit with endogenous rat beta and gamma subunits and the ability of aggregated Fc epsilon RI alpha subunits to mediate a variety of biochemical events. The signal transduction events monitored include phosphoinositide hydrolysis, Ca2+ mobilization, tyrosine phosphorylation, histamine release, and arachidonic acid metabolism. In all cases, the events mediated by aggregating human Fc epsilon RI alpha subunits were indistinguishable from those produced via the rat Fc epsilon RI alpha. These results demonstrate that the human Fc epsilon RI alpha subunit can functionally substitute for the rat Fc epsilon RI alpha subunit during signal transduction. The availability of this cell line will provide a means of evaluating potential Fc epsilon RI antagonists.
Gilfillan
A M
AM
Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Kado-Fong
H
H
Wiggan
G A
GA
Hakimi
J
J
Kent
U
U
Kochan
J P
JP
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006636:Histamine Release; D007073:Immunoglobulin E / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011961:Receptors, Fc / Q000235:genetics / Q000502:physiology*; D017455:Receptors, IgE; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D007295:Inositol Phosphates; D011961:Receptors, Fc; D017455:Receptors, IgE; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D014443:Tyrosine; D002118:Calcium