In vivo Evidence for Partial Activation of Eosinophils via the Histamine H 4 -Receptor: Adoptive Transfer Experiments Using Eosinophils From H 4 R -/- and H 4 R +/+ Mice.

Our previous in vitro studies revealed that histamine via histamine the H4 -receptors (H4 R), as compared to other stimuli, such as eotaxin or formylpeptides, rather partially activates eosinophilic granulocytes (eosinophils). In order to evaluate the H4 R-mediated activation of eosinophils in vivo , we employed dextran sodium sulfate (DSS)-induced colitis in mice, closely resembling human ulcerative colitis (UC), which is largely characterized by a local eosinophilic infiltration of the colon. IL-5-deficient BALB/c mice served as a model with reduced endogenous numbers of eosinophils, in which wild-type (H4 R+/+ ) or H4 R-deficient (H4 R-/- ) eosinophils were adoptively transferred during the course of DSS-induced colitis. During the 1-week observation period, transfer of eosinophils transiently reversed the acute clinical colitis-like phenotype (body weight loss, perianal bleeding, soft stool consistency) resulting from IL-5-deficiency. This reversion was significantly more pronounced upon transfer of eosinophils from H4 R+/+ mice as compared to those from H4 R-/- mice. Already at the end of the observation period, the clinical effects of the transfer of H4 R+/+ and H4 R-/- eosinophils became similar, as were the results of the histological examination of the cola and the analyses of cytokine production in cola and in re-stimulated lymph node cells performed at this time. Thus, analyzing clinical and pathological parameters representative of colitis in this model, we demonstrate that as well as in vitro , also in vivo histamine via the H4 R only partially activates eosinophils.