Different reasons have been advocated to explain these Etidronate discrepancies. Finally, the detection of TF mRNA in purified eosinophils could be due to non-specific amplification during the late cycles of PCR or contamination of the eosinophil fraction with monocytes, as hypothesized by Sovershaev et al.. However, in the present study this last possibility is unlikely given the high purity of our eosinophil preparations. In our experiments, we have compared three different antibodies to TF and we have chosen the most efficient in TF binding to test blood eosinophils. The observation that immunoreactivity for TF in purified eosinophils was variable in different subjects being almost absent in 2 out of 9 normal controls renders unlikely a non-specific binding of the antibody and supports interindividual differences in TF expression. In contrast, a strong reactivity was observed in 8 out of 9 patients with hypereosinophilic conditions. We cannot exclude that part of the TF detected in purified eosinophils is the result of uptake of monocyte-derived TF; however, the detection of TF mRNA in purified eosinophils suggests that it is, at least in part, produced by eosinophils themselves. The very high level of TF mRNA detected in eosinophils from one patient with idiopathic hypereosinophilic syndrome indicates that TF production by eosinophils is variable and can be markedly increased in pathological conditions. The reasons of the enhanced TF expression by blood eosinophils from patients with hypereosinophilia are as yet unknown; however, a candidate effector molecule may be interleukin-5 due to its pivotal role in promoting survival and activation of eosinophils. Future studies are Ginsenoside-Ro needed to investigate whether stimulation of eosinophils with IL-5 upregulates TF expression. Previously, we demonstrated by immunohistochemical methods that TF is expressed by inflammatory cells present in the infiltrate of chronic urticaria skin lesions. The nature of the TFexpressing cell was revealed by performing double-staining studies that showed co-localization of TF and eosinophil cationic protein, a classic cell marker of the eosinophil. The strong expression of TF in chronic urticaria lesional skin may be due to eosinophil activation, even if patients with chronic urticaria virtually never show peripheral eosinophilia, probably because TF specifically facilitates the early transendothelial migration of 
the eosinophils. Further immunohistochemical studies, carried out in patients with bullous pemphigoid, an autoimmune blistering disease characterized by skin and peripheral blood eosinophilia, showed a strong TF expression in lesional skin. Immunofluorescence studies using laser scanning confocal microscopy showed that, in patients with bullous pemphigoid, most of the cells making up the inflammatory infiltrate co-expressed TF and the eosinophil marker CD125, thus indicating that they were eosinophils. Considering that TF is the main activator of blood coagulation, the demonstration that eosinophils produce and store TF raises the possibility that they are involved in coagulation activation. Thus, they may contribute to induce thrombosis, even if other eosinophil-related pathophysiologic mechanisms may be operating, including endothelium damage and platelet activation. Eosinophils may damage endothelial cells by releasing peroxidase, and stimulate platelet activation and aggregation through several additional proteins contained in their granules, such as eosinophil cationic protein and major basic protein.