Migration of Jurkat cells in response to CypA

Abstract

Cyclophilins (CyPs) are ubiquitously distributed proteins, identified initially as the main binding target for cyclosporine A (CsA). A potential contribution of cyclophilin in inflammatory diseases is suggested from several studies. The activities of secreted cyclophilins are related to interactions with CD147, a transmembrane glycoprotein that plays a major role in lymphocyte migration and activation and is a binding partner to the β1 integrin. Our hypothesis is that the CypA/CD147/β1 interaction is important in mediating cellular migration in inflammation. Using Jurkat cells as our model, we first started by optimizing Jurkat cells adhesion, spreading and migration.In timelapse migration studies, Jurkat cells replated on fibronectin‐collagen I and poly‐lysine showed an increase in velocity by 3 folds when CypA was added to the media. The velocity of these cells significantly decreased when CD147 antibody (Ab) was added, compared to the corresponding isotype control. However, some element of CypA activation remained in the presence of CD147 Ab and it was not concentration dependent. Adding the CD147 Ab without prior CypA exposure did not have a significant effect. This suggests that the CypA‐CD147 activation might involve the β1 integrin. A β1 integrin blocking Ab combined with CD147 Ab is expected to completely prevent the CypA activation and the cell migration.Grant Funding Source: R56AI081152