Thy‐1 (CD90) regulates the extravasation of leukocytes during inflammation

Abstract

Human Thy-1 (CD90) has been shown to mediate adhesion of inflammatory cells to activated microvascular endothelial cells via interaction with Mac-1 (CD11b/CD18) in vitro. Since there are no data showing the physiological relevance of Thy-1 for the recruitment of inflammatory cells in vivo, different inflammation models were investigated in Thy-1-deficient mice and littermate controls. In thioglycollate-induced peritonitis, the number of neutrophils and monocytes was significantly diminished in Thy-1-deficient mice. During acute lung inflammation, the extravasation of eosinophils and monocytes into the lung was significantly reduced in Thy-1-deficient mice. Moreover, during chronic lung inflammation, the influx of eosinophils and monocytes was also strongly decreased. These effects were independent of Thy-1 expression on T cells, as shown by the transplantation of WT BM into the Thy-1-deficient mice. In spite of the strong Thy-1 expression on T cells in the chimeric mice, the extravasation of the inflammatory cells in these mice was significantly diminished, compared to control mice. Finally, the altered number and composition of infiltrating leukocytes in Thy-1-deficient mice modified the chemokine/cytokine and protease expression at the site of inflammation. In conclusion, Thy-1 is involved in the control of inflammatory cell recruitment and, thus, also in conditioning the inflammatory microenvironment.Key words: Extravasation . Inflammation . Thy-1 Supporting Information available online IntroductionThe recruitment of inflammatory cells to sites of inflammation plays an important role in the pathogenesis of several inflammatory diseases. Leukocyte adhesion to endothelial cells (ECs) follows a multistep process, including the capture of free leukocytes out of the blood stream, rolling, firm adhesion, and transendothelial diapedesis. The importance of several adhesion molecules in this series of events has been described previously [1]. In ICAM-1-deficient mice, neutrophil recruitment was significantly reduced, but it was not completely blocked in a chemical peritonitis model or in a lipopolysaccharide 645(LPS)-induced airway inflammation model, indicating the involvement of additional adhesion molecules [2,3]. Furthermore, leukocyte recruitment in experimental colitis was not affected by blocking ICAM-1 or MadCAM, whereas the blocking of VCAM-1 resulted in a significant attenuation of colitis [4]. Thus, under specific inflammatory conditions, certain adhesion molecules mediate adhesion and transmigration of leukocytes into the perivascular tissue.Recently, human Thy-1 expressed on ECs was identified as an adhesion molecule mediating the binding of neutrophils and monocytes to activated microvascular ECs [5]. Thy-1 is a highly glycosylated GPI-anchored surface protein and a member of the immunoglobulin superfamily [6,7,8]. In humans, Thy-1 is expressed on ECs at sites of inflammation or in tumours whereas ECs do not express Thy-1 in healthy tissue [5,9]. Thy-1 is also expressed on fibroblasts, neurons, and a su...

Thy-1 (CD90) Is an Interacting Partner for CD97 on Activated Endothelial Cells

“…The physiological relevance of Thy-1 in activated EC for the recruitment of inflammatory cells was demonstrated very recently in thioglycollate-induced peritonitis and acute and chronic lung inflammation using Thy-1-deficient mice (29). In this study, Thy-1 mediated the adhesion of granulocytes and monocytes to activated EC.…”

“…This interaction plays a pivotal role in the control of the emigration of granulocytes and monocytes from blood into peripheral tissue during inflammation. Consequently, the altered number and composition of extravasated leukocytes affect the inflammatory tissue microenvironment, including the chemokine/cytokine and protease pattern (29).…”

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

“…CD90 is a member of the immunoglobulin superfamily (7) and as such, like other adhesion molecules, is involved in cellcell adhesion and the recruitment of leukocytes via Mac-1 (CD11b/CD18) (29). It has been shown that CD90 is expressed by activated ECs (9,15,30).…”

Identification of molecular pathways involved in oxaliplatin-associated sinusoidal dilatation

“…Although endothelial cells do not express THY1 in healthy tissues, it is expressed on endothelial cells at inflammation sites or in tumors [24,25]. THY1 increases leukocyte adhesion to endothelial cells and transendothelial diapedesis [26]. In a rat model of sinusoidal obstruction syndrome, leukocyte adherence to the endothelial wall was increased, as was the phagocytic activity of hepatic macrophages [27].…”