Histamine induces microglia migration via
(A) Within the range of concentrations tested, only 100 μM histamine significantly induced microglia motility. Moreover, 10 μg/ml histamine-loaded PLGA microparticles (μP, 10 μg/ml) mimicked the effect of 100 μM histamine, whereas blank microparticles did not enhance motility. (B) Histamine-induced motility was inhibited in the presence of H4R antagonist (Ant H4R: JNJ7777120, 5 μM). Accordingly, H4R agonist application (Ag H4R: 4-methylhistamine dihydrochloride, 20 μM) resembled histamine treatment. The involvement of other receptors was excluded since the application of their respective antagonists did not interfere with the migration-inducing effect of histamine [H1R antagonist (mepyramine maleate), 1 μM; H2R antagonist (cimetidine), 5 μM; H3R antagonist (carcinine ditrifluoroacetate), 5 μM)]. (C) Representative photomicrographs depict the migratory effect induced by histamine and H4R agonist in N9 microglia cell line, an effect abolished in the presence of the H4R antagonist. Data are expressed as mean ± SEM (n = 3-20) and as mean total number of cells migrating across the scratch wound (*p < 0.05, **p < 0.01, ***p < 0.001, using Bonferroni’s multiple comparison test).