Tumor necrosis factor alpha potentiates the increase in cytosolic free calcium induced by bradykinin in guinea-pig tracheal smooth muscle cells.
The ability to respond to bradykinin (BK) by a bronchospasm is one of the most intriguing characteristics observed in asthmatic patients but not in healthy subjects. The molecular basis of this sensitivity is not yet known. Therefore, we studied the effect of BK, and its putative modulation by tumor necrosis factor alpha (TNF alpha), on cytosolic free Ca2+ concentration ([Ca2+]i) in fura-2-loaded tracheal smooth muscle cells in culture. BK induced a concentration-dependent rise in [Ca2+]i at concentrations between 10(-13) and 10(-11) M which was mediated via BK receptors of the B2 subtype. The net increase in [Ca2+]i induced by 10(-12)M BK was 478 +/- 52 nM. Pre-treatment of the cells with TNF alpha (10 ng/ml) for 24 h significantly potentiated this net increase in [Ca2+]i to 956 +/- 154 nM. The presence of anti-TNF alpha antibodies inhibited this potentiation. These results show that TNF alpha is able to interact with airway smooth muscle cells which suggests the existence of receptors for TNF alpha on these cells. The study, in vivo, of such interaction should help to further elucidate the mechanisms involved in airway hyperresponsiveness.
Amrani
Y
Y
INSERM CJF 91-05, Laboratoire de Neuro-immuno-pharmacologie, Université Louis-Pasteur I, Illkirch, France.
Bronner
C
C
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis*; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D009130:Muscle, Smooth / Q000166:cytology; D014132:Trachea / Q000033:anatomy & histology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D001920:Bradykinin; D002118:Calcium