ABSTRACT
In prior studies aggregation of the high affinity receptors for IgE, Fc epsilon RI, on a rat mast cell line, RBL-2H3, stimulated transcription of the gene for monocyte chemotactic protein-1 (MCP-1) and secretion of the protein. Unexpectedly, those delayed events appeared much less constrained by kinetic proofreading than had been documented for other receptor-initiated responses. The results of the present experiments are consistent with the proposal that the biosynthesis and secretion of MCP-1 result from a soluble messenger formed in the reaction cascades initiated by the receptor, and that Ca(2+) could serve as that messenger. Interestingly, whereas receptor-mediated signals were required for transcription of the gene for MCP-1 and secretion of the chemokine, such signals were not required for the intervening step of translation of its mRNA.
Subject(s)
Chemokine CCL2/biosynthesis , Chemokine CCL2/metabolism , Receptors, IgE/physiology , Animals , Calcium/metabolism , Calcium Signaling/drug effects , Calcium Signaling/immunology , Chemokine CCL2/genetics , Dactinomycin/pharmacology , Enzyme-Linked Immunosorbent Assay/methods , Intracellular Fluid/drug effects , Intracellular Fluid/metabolism , Kinetics , Ligands , Phospholipase C gamma , Phosphorylation , Protein Biosynthesis/immunology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Receptor Aggregation/immunology , Receptors, IgE/metabolism , Transcription, Genetic/drug effects , Transcription, Genetic/immunology , Tumor Cells, Cultured , Type C Phospholipases/physiology , Tyrosine/metabolismABSTRACT
Identification of the major components, how these interact with each other, and the modifications that follow in the sequence of events triggered by the receptor with high affinity for IgE, is progressing rapidly. A new challenge is to understand these interactions quantitatively. We present the fundamentals of the mechanistic model we are testing through mathematical modeling. The object is to see if the predictions of the model fit with the experimental results.
