Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells.
Nasal epithelial cells represent the first barrier against noxious agents and allergens. In allergic rhinitis, these cells are activated and histamine may be involved in this activation. Loratadine and one of its active metabolites, descarboethoxyloratadine, were studied for their ability to reduce the activation of nasal epithelial cells by histamine. Nasal turbinates or polyps were removed during surgery from 19 subjects, and nasal epithelial cells were recovered after enzymatic digestion. The in vitro activation of epithelial cells with histamine using an optimal dose (1 microM) and an optimal time (24 h) of incubation was studied, and the effect of loratadine or descarboethoxyloratadine (10 microM) was investigated. The expression of membrane markers (intercellular adhesion molecule-1 (ICAM-1) and a human leukocyte class II antigen (HLA-DR) was assessed by immunocytochemical analysis using an alkaline-antialkaline phosphatase (APAAP) system. The spontaneous expression of both markers was not significantly different in cells recovered from nasal turbinates or polyps, and there was a highly significant increase in the numbers of cells expressing ICAM-1 and HLA-DR following incubation with histamine. Loratadine or descarboethoxyloratadine significantly blocked these effects. This study shows a new possible antiallergic effect of H1-blockers and suggests that their effects on epithelial cells may be relevant in vivo.
Vignola
A M
AM
Clinique des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier, France.
Crampette
L
L
Mondain
M
M
Sauvère
G
G
Czarlewski
W
W
Bousquet
J
J
Campbell
A M
AM
D000328:Adult; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D017336:Loratadine / Q000494:pharmacology* / Q000031:analogs & derivatives; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014420:Turbinates / Q000187:drug effects / Q000276:immunology
D006684:HLA-DR Antigens; D006634:Histamine H1 Antagonists; D010880:Piperidines; D011725:Pyridines; D018799:Intercellular Adhesion Molecule-1; D017336:Loratadine; D006632:Histamine; C121345:desloratadine