Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H-1 receptors

Citation
M. Triggiani et al., Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H-1 receptors, J IMMUNOL, 166(6), 2001, pp. 4083-4091
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
166
Issue
6
Year of publication
2001
Pages
4083 - 4091
Database
ISI
SICI code
0022-1767(20010315)166:6<4083:HIEAIP>2.0.ZU;2-T
Abstract
Increasing evidence suggests that a continuous release of histamine from ma st cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages, In the present study histamine (10(-9)-10(-6) M) increased in a concentration-dep endent fashion the basal release of beta -glucuronidase (EC50 = 8.2 +/- 3.5 x 10(-9) M) and IL-6 (EC50 = 9.3 +/- 2.9 x 10(-8) M) from human lung macro phages, Enhancement of beta -glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2 -6 h of incubation. These effects were reproduced by the H-1 agonist (6-[2- (4-imidazolyl)ethylamino]-iv-(4-trifluoromethylphenyl)heptane carboxamide b ut not by the H-2 agonist dimaprit. Furthermore, histamine induced a concen tration-dependent increase of intracellular Ca2+ concentrations ([Ca2+](i)) that followed three types of response, one characterized by a rapid increa se, a second in which [Ca2+](i) displays a slow but progressive increase, a nd a third characterized by an oscillatory pattern. Histamine-induced beta -glucuronidase and IL-6 release and [Ca2+](i) elevation were inhibited by t he selective H-1 antagonist fexofenadine (10(-7)-10(-4) M), but not by the H-2 antagonist ranitidine. Inhibition of histamine-induced beta -glucuronid ase and IL-6 release by fexofenadine was concentration dependent and displa yed the characteristics of a competitive antagonism (K-d = 89 nM). These da ta demonstrate that histamine induces exocytosis and IL-6 production from h uman macrophages by activating H-1 receptor and by increasing [Ca2+](i) and they suggest that histamine may play a relevant role in the long-term sust ainment of allergic inflammation in the airways.