CD157 is a GPI-anchored ectoenzyme belonging to the NADase/ADP-ribosyl cyclase gene family involved in the control of neutrophil polarization, migration and diapedesis. In this study we investigated the role exerted by CD157 in human monocytes transendothelial migration and adhesion to extracellular matrix proteins. The results demonstrated that i) CD157 is expressed by virtually all circulating monocytes and its expression rapidly increases upon activation with MCP-1, and that ii) anti-CD157 monoclonal antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen, but CD157 antibody-induced crosslinking is sufficient to overcome the block suggesting an active signalling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β1 and β2 integrin, which, in turn, leads to the formation of a multimolecular complex favouring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor, despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK pathway, resulting in increased activity of the MAPK-ERK1/2 and the PI3K/Akt downstream signalling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signalling competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrins partnership provides optimal adhesion and transmigration of human monocytes.
The CD157-integrins partnership orchestrates human monocyte adhesion and transendothelial migration
PARROTTA, ROSSELLA;LO BUONO, NICOLA;MORONE, SIMONA;GIACOMINO, ALICE;BOVINO, PAOLA;NACCI, GIULIA;ORTOLAN, Erika;FERRERO, Enza;MALAVASI, Fabio;FUNARO, Ada
2011-01-01
Abstract
CD157 is a GPI-anchored ectoenzyme belonging to the NADase/ADP-ribosyl cyclase gene family involved in the control of neutrophil polarization, migration and diapedesis. In this study we investigated the role exerted by CD157 in human monocytes transendothelial migration and adhesion to extracellular matrix proteins. The results demonstrated that i) CD157 is expressed by virtually all circulating monocytes and its expression rapidly increases upon activation with MCP-1, and that ii) anti-CD157 monoclonal antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen, but CD157 antibody-induced crosslinking is sufficient to overcome the block suggesting an active signalling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β1 and β2 integrin, which, in turn, leads to the formation of a multimolecular complex favouring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor, despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK pathway, resulting in increased activity of the MAPK-ERK1/2 and the PI3K/Akt downstream signalling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signalling competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrins partnership provides optimal adhesion and transmigration of human monocytes.
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