The Bernd Sterzel - Lecture

The infiltration of inflammatory leukocytes to sites of tissue injury is governed by a concerted interaction of locally generated chemotactic molecules and adhesion molecules. Amongst the chemotactic molecules the family of chemotactic cytokines i.e. the chemokines have taken center stage during the last decade. In the kidney essentially all cell types i.e. endothelial, mesangial and epithelial cells can generate chemokines with specificity for polymorpho-nuclear leukocytes, T cells and monocyte-macrophages upon appropriate stimulation. Stimuli include almost any type of cell stress, such as immune complexes, complement activation, proinflammatory cytokines (e.g. TNF-a, IL-I, IFN-g) ischemia-reperfusion injury, reactive oxygen species and vasoactive agents etc. The various chemokines in turn activate the specific class of leukocytes bearing the complementary chemokine receptors causing their firm adhesion to the endothelium overlying the site of tissue injury and their subsequent migration to this site following the chemokine gradient.