Desensitization of IL-4 secretion from mouse bone marrow-derived mast cells.
Several recent findings indicate that mouse bone marrow-derived mast cells (BMMC) express RNA encoding interleukin-4 (IL-4) and secrete detectable amounts of IL-4 in response to cross-linking of Fc epsilon RI receptors, Fc gamma R receptors, or to ionomycin. We investigated the desensitization of BMMC from the view point of both IL-4 secretion and histamine release. In a desensitization protocol, the cells were challenged with an optimal concentration of antigen (10 ng/ml of DNP33-BSA) in the absence of calcium for various periods of time followed by addition of calcium to determine the loss in ability to release histamine or IL-4. In the context of histamine release, BMMC were desensitized completely in 45 min (T1/2 approximately 5 min). By contrast, in the context of IL-4 secretion, BMMC were only partly desensitized (52 +/- 5% of the control response) after 1 h of desensitization. A longer-term (2-6 h) desensitization of BMMC did not result in complete inhibition of IL-4 secretion (44 +/- 5% of control after 6 h). Northern blot analysis showed that IL-4 mRNA accumulation was decreased after a 1 h desensitization (37% +/- 14% of non-desensitized cells), suggesting that desensitization of IL-4 release results from a decrease in the amount of mRNA accumulation. These and other data support the view that the IgE-mediated signal transduction cascade has meditor-specific pathways that are independently regulated by homeostatic mechanisms within mast cells.
Nakamura
M
M
Johns Hopkins University, Asthma and Allergy Center, Baltimore, MD 21224.
MacGlashan
D
D
D000818:Animals; D015152:Blotting, Northern; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006636:Histamine Release / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D015847:Interleukin-4