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Migratory responses of polymorphonuclear leukocytes to kinin peptides
I Paegelow1, S Trzeczak, S Böckmann
1Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Rostock, Germany. inge.paegelow@med.uni-rostock.de
Pharmacology
|October 10, 2002
Summary
This study shows that kinin receptors B1 and B2 influence human neutrophil migration in vitro. Leukotriene B4 (LTB4) plays a role downstream, and B1 receptors appear active under normal physiological conditions.
Area of Science:
- Immunology
- Pharmacology
Background:
- Kinin receptors play a role in inflammatory responses.
- Neutrophil migration is crucial for innate immunity.
Purpose of the Study:
- To investigate the role of kinin receptors (B1 and B2) in human polymorphonuclear leukocyte migration.
- To elucidate the downstream signaling pathways involved in kinin-induced neutrophil chemotaxis.
Main Methods:
- In vitro study using the Boyden chamber technique for neutrophil migration.
- Checkerboard analysis to characterize chemotaxis.
- Pharmacological inhibition using specific B1 and B2 receptor antagonists and leukotriene B4 antagonist.
Main Results:
- Bradykinin, FR190997, des-Arg(9)-bradykinin, and des-Arg(10)-kallidin induced concentration-dependent neutrophil migration.
- B2 receptor antagonist HOE-140 inhibited bradykinin-induced migration, while B1 antagonist des-Arg(10)HOE-140 blocked des-Arg(9)-bradykinin and des-Arg(10)-kallidin effects.
- Leukotriene B4 (LTB4) antagonist ZK158252 inhibited LTB4, bradykinin, and des-Arg(10)-kallidin induced chemotaxis.
- Interleukin-1beta and IL-8 were not involved in bradykinin-induced migration.
Conclusions:
- B1 and B2 kinin receptors are involved in in vitro human neutrophil migration.
- LTB4 acts in the downstream pathway of kinin-induced neutrophil migration.
- B1 kinin receptors appear to be expressed under physiological conditions.