Premium
INFLAMMATORY CHEMOKINE CXCL5 EXPRESSION BY ENDOTHELIAL CELLS IS DEPENDENT UPON KININ B1 RECEPTOR ACTIVATION
Author(s) -
Duchene Johan,
Lecomte Florence,
Perretti Mauro,
Ahluwalia Amrita
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a702-c
Subject(s) - chemokine , kinin , receptor , cxcl5 , umbilical vein , agonist , interleukin 8 , cytokine , microbiology and biotechnology , receptor antagonist , immunology , chemistry , biology , antagonist , biochemistry , in vitro , bradykinin
The kinin B1 receptor is a major determinant of cytokine (ie interleukin‐1β (IL‐1β))‐induced leukocyte recruitment. However, the exact mechanism involved in this response is unclear. Recently, we showed that chemokines, in particular CXCL‐5, play a crucial role in this response but the exact site of B1 receptor expression and source of CXCL‐5 remained uncertain. The aim of the present study was to investigate the interaction between the B1 receptor and CXCL‐5 in endothelial cells and the participation of this pathway in leukocyte recruitment. Treatment of HUVECs (Human Umbilical Vein Endothelial Cells), with IL‐1β (1ng/ml, 4h) enhanced CXCL‐5 mRNA expression (~7‐fold vs NaCl; P<0.05). However, pretreatment with a B1 receptor antagonist (Lys‐Des‐Arg9[Leu]8BK, 10‐5 M) suppressed this response by ~30% (P<0.05). To verify that CXCL‐5 production is a direct effect of B1 receptor activation, HUVECs were treated with B1 receptor agonist (Lys‐Des‐Arg9 BK; 10‐9 ‐ 10‐5 M). Indeed, CXCL‐5 mRNA expression increased dose‐dependently in response to the agonist. Finally, using the intravital microscopy technique, we showed that pretreatment with a selective neutralizing CXCL‐5 antibody (20μg/mouse, 30min pretreatment, i.p.) significantly attenuated IL‐1β (5ng ip, 4h)‐induced leukocyte emigration by ~30%. Taken together, these results suggest that CXCL‐5 released from endothelial cells likely plays a role in B1 receptor mediated neutrophil recruitment. Moreover these studies confirm and extend our understanding of the role of kinin B1 receptor in inflammatory cell recruitment. This work is supported by the British Heart Foundation.