Using a thioglycollate-induced peritonitis model and an acute as well as chronic lung inflammation model, we demonstrate that Thy-1 plays an important role in the control of leukocyte recruitment at sites of inflammation and in the conditioning of the inflammatory tissue microenvironment. Because Thy-1 displays a species-specific expression Sunitinib in vitro pattern 6, 17, 18, we analysed Thy-1 expression on ECs at sites of inflammation in mice. In healthy lung or healthy peritoneal tissue, Thy-1 was only hardly detectable on few ECs (Fig. 1A and B). In contrast to humans, Thy-1 seems to be slightly expressed
on resting ECs in mice. However, upon induction of inflammation, Thy-1 expression on ECs was massively enhanced (Fig. 1C–F). We found strong Thy-1 expression on ECs of WT mice during lung inflammation, induced by immunization with OVA (Fig. 1D and F). In addition, Thy-1 was expressed on ECs in peritoneal tissue upon induction of inflammation, induced by thioglycollate (Fig. 1C and E). The functional role of Thy-1 in mediating adhesion and transmigration of neutrophils and monocytes was studied in a thioglycollate-induced peritonitis model in Thy-1−/− mice Palbociclib supplier and littermates. Prior
to induction of inflammation, the blood leukocyte count as well as the subset proportions in Thy-1−/− mice and control mice were similar (Table 1). Induction of inflammation by i.p. injection of thioglycollate
induced strong recruitment of leukocytes into the peritoneal cavity (Fig. 2A), which MRIP peaked 24 h after injection. The number of emigrated leukocytes was significantly decreased at 6 and 24 h after the i.p. injection in Thy-1−/− mice, compared to WT littermates. At later time points, no significant differences in the influx of inflammatory cells into the peritoneal cavity in Thy-1−/− and WT mice were detected (Fig. 2A). Analysis of extravasated cells 24 h after thioglycollate injection revealed that the recruitment of neutrophils and monocytes was significantly reduced in Thy1−/− mice (Fig. 2B). Lymphocytes were only marginally detectable. Histological analysis of peritoneal tissue confirmed these data. In contrast to those in Thy-1−/− mice, inflammatory cells in WT mice could be observed by H&E staining (Fig. 2C and D). Using immunohistochemical staining, a clear infiltration of CD11b+ cells was detected in the peritoneal tissue of WT mice (Fig. 2G). In Thy1−/− mice the infiltration was significantly inhibited (Fig. 2H). Further analysis of these infiltrates revealed that F4/80+macrophages (Fig. 2I and J) and Gr-1+neutrophil granulocytes (Fig. 2K and L) were decreased in peritoneal tissue of Thy1−/− mice. Taken together, Thy-1 plays an important role in the recruitment of neutrophils and monocytes during thioglycollate-induced peritoneal inflammation.