Original ArticlesUp-regulation of the urokinase-type plasminogen activator receptor by monocyte chemotactic proteinsNakayama, M.; Yoshida, E.; Sugiki, M.; Anai, K.; Maruyama, M.; Mihara, H.Author Information The authors are with the Department of Physiology, Miyazaki Medical College, Miyazaki, Japan. (Received 20 November 2001; revised 19 February 2002; accepted 20 February 2002) Address correspondence to Etsuo Yoshida, Department of Physiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. Fax: (+81) 985 857932; e-mail: [email protected] Blood Coagulation & Fibrinolysis: July 2002 - Volume 13 - Issue 5 - p 383-391 Buy Abstract The urokinase-type plasminogen activator receptor (uPAR) is a multifunctional molecule involved in migration and adhesion of leukocytes to sites of inflammation. Based on our hypothesis that a chemoattractant can stimulate uPAR expression by its target cell, thereby promoting cell migration, we employed three chemokines [monocyte chemotactic protein (MCP)-1, MCP-2 and MCP-3] as chemoattractants, and examined their effect on uPAR expression in a human monocyte-like cell line, U937. Northern blot analysis demonstrated that all three chemokines tested increased the level of uPAR mRNA in time-dependent and dose-dependent manners. Among them, MCP-3 exhibited the most potent effect. Scatchard analysis showed that incubation with MCP-3 (1 × 10−8 mol/l) for 16 h resulted in a significant increase in the number of uPAR from (6.8 ± 0.3) × 103 to (10.3 ± 1.6) × 103/cell, and in a slight increase in the equilibrium dissociation constant, Kd. The effect of anti-uPAR antibodies on MCP-3-induced U937 cell migration across an endothelial cell monolayer and a type I collagen layer was assessed by means of the modified Boyden chamber assay. Although MCP-3 caused a three-fold increase in migration, incubation with an antibody to uPAR markedly abrogated the induced cell migration. These results support our hypothesis and suggest that up-regulation of uPAR in target cells might be an important and common feature of chemoattractants. © 2002 Lippincott Williams & Wilkins, Inc.