BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: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 humanCBMCs by using flow cytometric analysis. RESULTS:HumanCBMCs 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 humanCBMCs. CONCLUSION: 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.
Authors: Travis W Faber; Nicholas A Pullen; Josephine F A Fernando; Elizabeth Motunrayo Kolawole; Jamie J A McLeod; Marcela Taruselli; Kathryn L Williams; Kevin O Rivera; Brian O Barnstein; Daniel H Conrad; John J Ryan Journal: Cell Immunol Date: 2014-05-21 Impact factor: 4.868
Authors: Eric Pasmant; Julien Masliah-Planchon; Pascale Lévy; Ingrid Laurendeau; Nicolas Ortonne; Béatrice Parfait; Laurence Valeyrie-Allanore; Karen Leroy; Pierre Wolkenstein; Michel Vidaud; Dominique Vidaud; Ivan Bièche Journal: Mol Med Date: 2010-09-10 Impact factor: 6.354
Authors: Kelly Speiran; Daniel P Bailey; Josephine Fernando; Matthew Macey; Brian Barnstein; Motunrayo Kolawole; Dana Curley; Stephanie S Watowich; Peter J Murray; Carole Oskeritzian; John J Ryan Journal: J Leukoc Biol Date: 2009-02-19 Impact factor: 4.962
Authors: Patrice Dubreuil; Sébastien Letard; Marco Ciufolini; Laurent Gros; Martine Humbert; Nathalie Castéran; Laurence Borge; Bérengère Hajem; Anne Lermet; Wolfgang Sippl; Edwige Voisset; Michel Arock; Christian Auclair; Phillip S Leventhal; Colin D Mansfield; Alain Moussy; Olivier Hermine Journal: PLoS One Date: 2009-09-30 Impact factor: 3.240