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Autocrine regulation of cord blood–derived human mast cell activation by IL-10☆

2001; Elsevier BV; Volume: 108; Issue: 1 Linguagem: Inglês

10.1067/mai.2001.115753

1097-6825

Bernard Royer, Sonia Varadaradjalou, Philippe Saas, Anne-Claude Gabiot, B Kantelip, Frédéric Féger, Jean‐Jacques Guillosson, Jean‐Pierre Kantelip, Michel Arock,

Food Allergy and Anaphylaxis Research

Ligation of the high-affinity receptor for IgE on human mast cells (MCs) induces the release of proinflammatory mediators, including vasoactive amines and cytokines (TNF-alpha, IL-5, and IL-8). Moreover, we have recently shown that IL-10 inhibits the release of proinflammatory mediators by activated MCs.We investigated whether human cord blood-derived MCs (CBMCs) could produce IL-10 and whether this production could inhibit their activation in an autocrine fashion.IL-10 synthesis by resting or activated human MCs derived from cord blood progenitors was investigated in cell supernatants or by using immunostaining and RT-PCR methods. In addition, the effect of IL-4 on such synthesis was also studied. Anti-IL-10-neutralizing antibodies were used to investigate the validity of the hypothesis of an autocrine regulation of MCs by IL-10. Finally, the presence of specific receptors for IL-10 was searched on human CBMCs by using flow cytometric analysis.Human CBMCs spontaneously synthesize and release IL-10, and this synthesis is increased after IgE/anti-IgE stimulation. In addition, the presence of IL-10 in resting or in activated MCs was proved by immunostaining. Interestingly, the release of IL-10 was also increased after incubation of the cells with IL-4. Besides, the use of neutralizing antibodies against IL-10 confirmed that IL-10 released inhibited MC activation in an autocrine fashion. Finally, the presence of specific receptors for this cytokine was observed on the membranes of our population of human CBMCs.Taken together, our data are in favor of an autocrine regulation pathway through synthesis and release of IL-10 by human MCs. Such an autoregulatory mechanism is, to our knowledge, the first described for these elements.