Leukocyte recruitment in response to inflammatory signals is in part governed by interactions between endothelial cell receptors belonging to the Ig superfamily and leukocyte integrins. In our previous work, the human Ig superfamily glycoprotein Thy-1 (CD90) was identified as an activation-associated cell adhesion molecule on human dermal microvascular endothelial cells. Furthermore, the interaction of Thy-1 with a corresponding ligand on monocytes and polymorphonuclear cells was shown to be involved in the adhesion of these leukocytes to activated Thy-1-expressing endothelial cells. In this study, we have identified the specific interaction between human Thy-1 and the leukocyte integrin Mac-1 (CD11b/CD18; αMβ2) both in cellular systems and in purified form. Monocytes and polymorphonuclear cells were shown to adhere to transfectants expressing human Thy-1 as well as to primary Thy-1-expressing human dermal microvascular endothelial cells. Furthermore, leukocyte adhesion to activated endothelium as well as the subsequent transendothelial migration was mediated by the interaction between Thy-1 and Mac-1. This additional pathway in leukocyte-endothelium interaction may play an important role in the regulation of leukocyte recruitment to sites of inflammation.

The expression of the avb3 integrin (CD51/CD61) on human melanoma cells has been shown to be associated most closely with tumor progression and metastases formation in melanoma. Here, we demonstrated a specific interaction of the avb3 integrin on melanoma cells with the human Thy-1, an inducible cell adhesion molecule expressed on the cell surface of activated endothelial cells (EC). The interaction was shown by the binding of purified Thy-1 protein to a V b 3 transfected cells, to avb3-expressing melanoma cells and to purified a V b 3 integrin. Moreover, melanoma cells adhere specifically to Thy-1 transfectants via avb3 on melanoma cells showing the functional relevance of this interaction for cell adhesion. Finally, the importance of the avb3/Thy-1 interaction for the adhesion of melanoma cells to the activated endothelium was confirmed under static and flow conditions by the inhibition of melanoma cell adhesion to and transmigration across activated EC by blocking the avb3/Thy-1 interaction. In conclusion, we have identified a new pair of adhesion molecules Thy-1 and avb3 mediating the interaction of melanoma cells and activated EC. These data explain at least in part the high tumorigenicity of avb3-expressing melanoma cells and the association of avb3-positive melanoma cells with a high risk of metastasis and poor prognosis.

The chronic inflammatory skin disease psoriasis is characterized by prominent skin infiltration by neutrophils and microabscess formation. The adhesion of leukocytes and subsequent transmigration through the activated endothelium is one prerequisite for the accumulation of these cells in skin. In recent studies, the human Thy-1 (CD90) was characterized as an adhesion molecule on activated endothelial cells (ECs) mediating the adhesion of neutrophils via the interaction with the beta2-integrin Mac-1. Based on these novel findings, we compared the roles of Thy-1 and ICAM-1 in the adhesion of neutrophils from patients with psoriasis to activated ECs. The adhesion of peripheral blood neutrophils of patients suffering from psoriasis to Thy-1-transfected cells as well as to activated, Thy-1-expressing human dermal microvascular ECs (HDMECs) is distinctly increased in comparison to the adhesion of neutrophils from healthy controls. In contrast, adherence of psoriatic neutrophils to ICAM-1 transfectants is, if at all, only slightly enhanced compared to healthy controls. The interaction of healthy as well as psoriatic polymorphonuclear cells to Thy-1 transfectants and HDMECs was significantly inhibited by blocking Thy-1 on ECs or its receptor Mac-1 on neutrophils, indicating the importance of this interaction for the adhesion of neutrophils to activated endothelium. In conclusion, our data indicate that the adhesion of neutrophils to activated ECs mediated by Thy-1/Mac-1 interaction is an important attachment mechanism facilitating their subsequent migration into lesional psoriatic skin.

IntroductionThe consumption of food is necessary for our everyday survival and is promoted by an intricate network of complex homeostatic and hedonic interactions. Hunger is a motivational state considered as an endpoint of these elements; it ensures that we actively seek out food when necessary. However, hunger is not only the result of simple energy deficiency; it has emerged as a product of a complex biopsychological and environmental interaction. Given the rapid development of obesity worldwide, a better understanding of the interaction between the encoding of food in the brain reward network and homeostatic energy regulation is of paramount importance for the development of new treatment strategies. BACKGROUND.Food intake is guided by homeostatic needs and by the reward value of food, yet the exact relation between the two remains unclear. The aim of this study was to investigate the influence of different metabolic states and hormonal satiety signaling on responses in neural reward networks.