Blockade of proteinase-activated receptor 4 inhibits neutrophil recruitment in experimental inflammation in mice

• Published in: Inflammation research 2014-11, Vol.63 (11), p.935-941
• Main Authors: Gomides, Lindisley F., Lima, Onésia C. O., Matos, Natália A., Freitas, Kátia M., Francischi, Janetti Nogueira, Tavares, Juliana Carvalho, Klein, André
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Biomedical and Life Sciences; Biomedicine; Carrageenan; Chemokine CXCL1 - immunology; Dermatology; Disease Models, Animal; Female; Immunology; Inflammation - chemically induced; Inflammation - immunology; Interleukin-8; Mice, Inbred BALB C; Neurology; Neutrophil Infiltration - drug effects; Oligopeptides - pharmacology; Original Research Paper; Pharmacology/Toxicology; Receptors, Thrombin - antagonists & inhibitors; Rheumatology
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-014-0767-8

Objective and design The activation of proteinase-activated receptors (PARs) has been implicated in the development of important hallmarks of inflammation, including in vivo leukocyte recruitment; however, its role in the regulation of leukocyte migration in response to inflammatory stimuli has not been elucidated until now. Here, we examined the effects of the PAR4 antagonist YPGKF-NH 2 (tcY-NH 2 ) on neutrophil recruitment in experimentally induced inflammation. Methods BALB/c mice were intrapleurally injected with tcY-NH 2 (40 ng/kg) prior to intrapleural injection of carrageenan (Cg) or neutrophil chemoattractant CXCL8; the number of infiltrating neutrophils was evaluated after 4 h, and KC production was assessed at different times after Cg injection. Neutrophil adhesion and rolling cells were studied using a brain circulation preparation 4 h after the Cg or CXCL8 challenge in tcY-NH 2 -treated mice. Results PAR4 blockade inhibited CXCL8- and Cg-induced neutrophil migration into the pleural cavity of BALB/c mice and reduced neutrophil rolling and adherence. Surprisingly, PAR4 blockade increased the level of KC in response to carrageenan. Conclusion These results demonstrated that PAR4 blockade impairs neutrophil migration in vivo, suggesting that PAR4 plays an important role in the regulation of inflammation, at least in part because of its ability to inhibit the actions of the neutrophil chemoattractant CXCL8.