TY - JOUR
T1 - Modulation of histamine release from mast cells by interleukin-2 is affected by nedocromil sodium
AU - Rubinchik, Evelina
AU - Norris, Alan
AU - Levi-Schaffer, Francesca
PY - 1995/7
Y1 - 1995/7
N2 - We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2 (IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects and nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 μg/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5-6 days) incubated with IL-2 (50 pg/ml). Nedocromil sodium was used at 10-5 M. Nedocromil sodium markedly inhibited the enhancing effect of IL-2 on compound 48/80 and anti-IgE mediated MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30-50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.
AB - We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2 (IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects and nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 μg/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5-6 days) incubated with IL-2 (50 pg/ml). Nedocromil sodium was used at 10-5 M. Nedocromil sodium markedly inhibited the enhancing effect of IL-2 on compound 48/80 and anti-IgE mediated MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30-50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.
KW - IL-2
KW - histamine release
KW - mast cells
KW - nedocromil sodium
UR - http://www.scopus.com/inward/record.url?scp=0028990909&partnerID=8YFLogxK
U2 - 10.1016/0192-0561(95)00041-Y
DO - 10.1016/0192-0561(95)00041-Y
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C2 - 8586484
AN - SCOPUS:0028990909
SN - 0192-0561
VL - 17
SP - 563
EP - 570
JO - International Journal of Immunopharmacology
JF - International Journal of Immunopharmacology
IS - 7
ER -