Histamine release from mast cells of EAE rats by Gi protein-dependent and IgE-dependent pathways.
We investigated both Gi protein-dependent and IgE-dependent pathways that control release of histamine by PMCs derived from EAE or Complete Freund's Adjuvant (CFA) immunized rats. The number and histamine content of MCs per rat were the same between normal and EAE rats. Activation of Gi pathway by substance P (SP), DSA, 48/80, and mastoparan resulted in a dose-dependent increase in release of histamine by PMCs in normal, EAE-, and CFA-immunized rats. In EAE and CFA rats, however, the induction was decreased by 10-20% compared to normal rats. The histamine release induced by MP was decreased at a concentration of 3 microM, but not at 10 microM in severe active EAE rats. Activation of the IgE pathway by MAM and concanavalin A (Con A) in the presence of phosphatidylserine led to dose-dependent histamine release in normal rats, and a 10-25% lower level of induction was observed in EAE rats. In CFA rats, the induction of histamine release was equivalent to normal rats. There was an increase in intracellular calcium stores following activation of both pathways in normal rats, whereas depletion of calcium stores by ryanodine reduced the level of induction by 48/80 and MP by 9-11% in normal rats. In EAE rats, 48/80, Con A, and MAM induced a smaller increase, but SP and MP induced larger or similar increases in calcium stores compared to normal rats. It was unlikely that the calcium stores of the PMCs from EAE rats were depleted, because MP stimulated calcium movement subsequent to the release of histamine. These results suggested that the Gi pathway may not be correlated to clinical manifestation of EAE, but cold be involved in the inflammatory process, and that the IgE pathway is better associated with clinical symptoms of EAE and may be more directly related to disease outcome.
Ichigi
J
J
Department of Molecular Pharmacology, Meiji College of Pharmacy, Tokyo, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D007073:Immunoglobulin E / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D010455:Peptides; D051381:Rats; D011917:Rats, Inbred Lew; D012433:Ryanodine / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D012433:Ryanodine; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; C037500:mastoparan; D006632:Histamine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium