Distinct effects of sphingosine-1-phosphate, lysophosphatidic acid and histamine in human and mouse dendritic cells.

Dendritic cells (DC) are specialized antigen presenting cells characterized by their ability to migrate into target sites and secondary lymphoid organs in order to process antigens and activate naive T cells. Previously, we have shown that several secretion products from platelets and mast cells such as histamine, sphingosine-1-phosphate (S1P), and lysophosphatidic acid (LPA) have chemotactic activity towards immature human DC. Furthermore, they limit the capacity of mature human DC to initiate and amplify T helper cell type 1 (Th1) immune responses by inhibition of interleukin (IL)-12 and upregulation of IL-10 secretion. In this study we focused on the effect of these agents on murine DC. In murine DC no influence on IL-10 and IL-12 release by these agents was observed. Moreover, histamine and LPA failed to stimulate chemotaxis and actin reorganization in mouse DC. Instead, S1P had chemotactic activity and induced actin polymerization in immature as well as mature mouse DC. Therefore, our in vitro data implicate that in contrast to humans the function and immunological capacity of murine DC are not so tightly controlled by mast cell and platelet-derived secretion products such as histamine, S1P and LPA. These findings suggest that mouse models might underestimate the complex regulative network between mast cells, platelets and DC.