Altered neutrophil homeostasis in kinin B1 receptor-deficient mice

The kallikrein-kinin system is activated during inflammation and plays a ma jor role in the inflammatory process. One of the main mechanisms of kinin a ction includes the modulation of neutrophil function employing both recepto rs for kinins, B1 and B2, In this report we show by the use of B1 receptor- deficient mice that neutrophil migration in inflamed tissues is dependent o n kinin B1 receptors, However, there is no change in circulating leukocyte number and composition after genetic ablation of this receptor. Furthermore , apoptosis of neutrophils necessary for the resolution of persistent infla mmatory processes is impaired in mice lacking the B1 receptor. We also show that this receptor is expressed on neutrophils, thus it may be directly in volved in the induction of apoptosis in these cells after prolonged activat ion at inflamed sites. In conclusion, our data show that the kinin B1 recep tor modulates migration and the life span of neutrophils at sites of inflam mation and may be therefore an important drug target in the therapy of infl ammatory diseases.