Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560

NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose-dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca2+]i.NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID.Migration is an important feature of leukocytes which represents a pre-requisite for normal leukocyte function in physiological processes such as protection against infection or foreign antigens. Under pathological conditions, leukocytes infiltrate tissue which locally produces pro-inflammatory substances and chemokines. This process is known as leukocyte recruitment. The normal ability for active movement is an important pre-requisite for the effective recruitment of leukocytes from the microvascular circulation [1]. The blockade of leukocyte migration can abrogate the process of leukocyte recruitment and inflammation. Therefore, the modulation of leukocyte migration has been proposed as a potential therapeutic approach for the treatment of several inflammatory diseases such as psoriasis, eczema, multiple sclerosis and arthritis [2,3].Dependent on the tissue structure, two types of non-directed leukocyte migration can be identified: two- and three-dimensional haptokinesis. Two-dimensional leukocyte haptokinesis can be found on two-dimensional surfaces, such as inner vessel walls, the peritoneum and the pleura. Three-dimensional haptokinetic migration occurs in the tissue which contains cellular or fibrillar extracellular matrix components promoting leukocyte movement [1]. Prevailing random haptokinetic leukocyte migration becomes directional (hapto- or chemotactic), if a gradient of ch