Toll-like receptors (TLRs) are a family of transmembrane receptors that have been preserved throughout evolution and which selectively recognize a broad spectrum of microbial components and endogenous molecules released by injured tissue. Identification of these ligands by TLRs triggers signalling pathways which lead to the expression of numerous genes involved in a defensive response. In mammals, the products of these genes initiate inflammation, coordinate the effector functions of innate immunity, instruct and modulate adaptive immunity and initiate tissue repair and regeneration. Different mutations and experimental models which alter TLR function have revealed the significance of these receptors in susceptibility to infection and their involvement in the pathogenesis of a large number of non-infective inflammatory disorders such as cancer, allergy, autoimmunity, inflammatory bowel disease, or atherosclerosis. TLRs are currently viewed as important targets for the development of new vaccines and innovative therapies to prevent and treat human diseases.

The quantitative measurement of the expression of both cytoplasmic and surface CD63 antigen by human mast cells from both normal and pathological bone marrow samples was studied by use of flow cytometry. Our major goal was to analyze whether in vivo CD63 expression by human bone marrow mast cells could be useful to discriminate bone marrow mast cells from patients with mastocytosis from other conditions. For that purpose, a total of 65 subjects corresponding to 12 healthy volunteers, 25 B‐cell chronic lymphoproliferative disorders, 5 reactive bone marrow samples, 4 myelodysplastic syndromes, and 19 mastocytosis were analyzed. The expression of both surface and cytoplasmic CD63 by human bone marrow mast cells is clearly demonstrated. Our results show that high amounts of CD63 are present in human bone marrow mast cells most of it corresponding to an intracellular localization. No significant differences in CD63 expression were observed as regards both total and cytoplasmic CD63, except for higher CD63 levels in adult patients with mastocytosis (P = 0.05). By contrast, the mean level of surface CD63 significantly varied between the different groups of individuals. Accordingly, patients with monoclonal gammopathies displayed a slight decrease (P = 0.1) in surface CD63 expression, whereas bone marrow mast cells from adults with indolent systemic mast cell disease showed significantly (P = 0.0005) higher levels of surface CD63 as compared to healthy controls. Cytometry (Comm. Clin. Cytometry) 34:223–228, 1998.