RT Journal Article
SR Electronic
T1 The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 589
OP 600
DO 10.1136/gutjnl-2013-305933
VO 64
IS 4
A1 Marco Genua
A1 Silvia D'Alessio
A1 Javier Cibella
A1 Alessandro Gandelli
A1 Emanuela Sala
A1 Carmen Correale
A1 Antonino Spinelli
A1 Vincenzo Arena
A1 Alberto Malesci
A1 Sergio Rutella
A1 Victoria A Ploplis
A1 Stefania Vetrano
A1 Silvio Danese
YR 2015
UL http://gut.bmj.com/content/64/4/589.abstract
AB Objective Inflammation plays crucial roles in the pathogenesis of several chronic inflammatory disorders, including Crohn's disease (CD) and UC, the two major forms of IBD. The urokinase plasminogen activator receptor (uPAR) exerts pleiotropic functions over the course of both physiological and pathological processes. uPAR not only has a key role in fibrinolysis but also modulates the development of protective immunity. Additionally, uPAR supports extracellular matrix degradation and regulates cell migration, adhesion and proliferation, thus influencing the development of inflammatory and immune responses. This study aimed to evaluate the role of uPAR in the pathogenesis of IBD. Design The functional role of uPAR was assessed in established experimental models of colitis. uPAR deficiency effects on cytokine release, polarisation and bacterial phagocytosis were analysed in colonic macrophages. uPAR expression was analysed in surgical specimens collected from normal subjects and patients with IBD. Results In mice, uPAR expression is positively regulated as colitis progresses. uPAR-KO mice displayed severe inflammation compared with wild-type littermates, as indicated by clinical assessment, endoscopy and colon histology. The absence of uPAR led to an increased production of inflammatory cytokines by macrophages that showed an M1 polarisation and impaired phagocytosis. In human IBD, CD68+ macrophages derived from the inflamed mucosa expressed low levels of uPAR. Conclusions These findings point to uPAR as an essential component of intestinal macrophage functions and unravel a new potential target to control mucosal inflammation in IBD.