Background: The chemokines monocyte chemoattractant factor-1, RANTES, and macrophage inflammatory protein-1 alpha release histamine from human basophils, as well as rat and mouse mast cells. The purpose of this investigation was to determine whether these chemokines release histamine from human skin mast cells in situ.
Methods: A microdialysis technique was used to measure histamine release in skin. First, the model was validated by using anti-IgE, codeine, and stem cell factor (SCF); then the histamine-releasing effects of the chemokines were investigated. A total of 47 skin specimens from 41 donors were investigated. Hollow microdialysis fibers were inserted intradermally, and each fiber was slowly perfused (3 microliters/min). Anti-IgE, codeine, SCF, or chemokines were injected intradermally above individual fibers, and dialysate was collected at 2-minute intervals for 20 minutes. Each series of investigations comprised five to eight single experiments.
Results: Anti-IgE (4 to 4000 U/ml), codeine (0.001 to 1 mg/ml), and SCF (5.4 x (10(-11) to 10(-8) mol/L)) released histamine in a dose-dependent manner; maximum histamine release was 97.4, 116.3, and 9.5 pmol/20 min, respectively. Monocyte chemoattractant factor-1, RANTES, and macrophage inflammatory protein-1 alpha in concentrations of 10(-10) to 10(-6) mol/L did not release histamine; histamine release by 10(-6) mol/L chemokine was less than 0.2 pmol/20 min. None of the chemokines modulated anti-IgE-induced histamine release. In contrast, SCF significantly potentiated anti-IgE-induced histamine release by 33%. All chemokines, but not SCF, released histamine from human basophils.
Conclusion: We conclude that the chemokines monocyte chemoattractant factor-1, RANTES, and macrophage inflammatory protein-1 alpha do not release histamine from human skin mast cells.