MIDKINE, A RETINOIC ACID-INDUCIBLE HEPARIN-BINDING CYTOKINE IN INFLAMMATORY RESPONSES - CHEMOTACTIC ACTIVITY TO NEUTROPHILS AND ASSOCIATIONWITH INFLAMMATORY SYNOVITIS

Midkine (MK) is a retinoic acid-inducible heparin-binding cytokine, In the inflammatory synovitis of rheumatoid arthritis and osteoarthritis , MK was detected in synovial fluid, synoviocytes, and endothelial cel ls of new blood vessels. Normal synovial fluid and noninflammatory syn ovial tissue did not contain detectable MK. Therefore, MK showed infla mmation-associated expression in these cases. Furthermore, MK was foun d to promote chemotaxis of neutrophils in the range of 10 ng/ml, The m ode of action of MK was found to be haptotactic; the substrate-bound f orm of MK was the active one, MK is also known to promote fibrinolysis . These activities of MK are in agreement with the modes of MK express ion in various pathological statuses, and thus MK is proposed to be an important molecule regulating inflammatory responses.