Altered neutrophil homeostasis in kinin B1 receptor-deficient mice.
The kallikrein-kinin system is activated during inflammation and plays a major role in the inflammatory process. One of the main mechanisms of kinin action includes the modulation of neutrophil function employing both receptors 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 on 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 inflammatory processes is impaired in mice lacking the B1 receptor. We also show that this receptor is expressed on neutrophils, thus it may be directly involved in the induction of apoptosis in these cells after prolonged activation at inflamed sites. In conclusion, our data show that the kinin B1 receptor modulates migration and the life span of neutrophils at sites of inflammation and may be therefore an important drug target in the therapy of inflammatory diseases.
Department of Biophysics, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
R C
RC
Araújo
R
R
Kettritz
I
I
Fichtner
A C
AC
Paiva
J B
JB
Pesquero
M
M
Bader
D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000502:physiology; D001772:Blood Cell Count; D002465:Cell Movement / Q000502:physiology; D004396:Coloring Agents; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000473:pathology; D011419:Propidium; D012333:RNA, Messenger / Q000096:biosynthesis; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017304:Annexin A5; D004396:Coloring Agents; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D011419:Propidium