Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines.
BACKGROUND
Angiotensin II (Ang II) is implicated in the development of cardiac ischemic disorders in which prominent neutrophil accumulation occurs. Ang II can be generated intravascularly by the renin-angiotensin system or extravascularly by mast cell chymase. In this study, we characterized the ability of Ang II to induce neutrophil accumulation.


RESULTS
Intraperitoneal administration of Ang II (1 nmol/L) induced significant neutrophil recruitment within 4 hours (13.3+/-2.3x10(6) neutrophils per rat versus 0.7+/-0.5x10(6) in control animals), which disappeared by 24 hours. Maximal levels of CXC chemokines were detected 1 hour after Ang II injection (577+/-224 pmol/L cytokine-inducible neutrophil chemoattractant [CINC]/keratinocyte-derived chemokine [KC] versus 5+/-3, and 281+/-120 pmol/L macrophage inflammatory protein [MIP-2] versus 14+/-6). Intravital microscopy within the rat mesenteric microcirculation showed that the short-term (30 to 60 minutes) leukocyte-endothelial cell interactions induced by Ang II were attenuated by an anti-rat CINC/KC antibody and nearly abolished by the CXCR2 antagonist SB-517785-M. In human umbilical vein endothelial cells (HUVECs) or human pulmonary artery media in culture, Ang II induced interleukin (IL)-8 mRNA expression at 1, 4, and 24 hours and the release of IL-8 at 4 hours through interaction with Ang II type 1 receptors. When HUVECs were pretreated with IL-1 for 24 hours to promote IL-8 storage in Weibel-Palade bodies, the Ang II-induced IL-8 release was more rapid and of greater magnitude.


CONCLUSIONS
Ang II provokes rapid neutrophil recruitment, mediated through the release of CXC chemokines such as CINC/KC and MIP-2 in rats and IL-8 in humans, and may contribute to the infiltration of neutrophils observed in acute myocardial infarction.
Nabah
Yafa Naim Abu
YN
Department of Pharmacology,Faculty of Medicine, University of Valencia, Valencia, Spain.
Mateo
Teresa
T
Estellés
Rossana
R
Mata
Manuel
M
Zagorski
John
J
Sarau
Henry
H
Cortijo
Julio
J
Morcillo
Esteban J
EJ
Jose
Peter J
PJ
Sanz
Maria-Jesus
MJ
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008643:Mesentery / Q000098:blood supply; D008833:Microcirculation / Q000502:physiology; D020556:Neutrophil Infiltration; D010529:Peritoneal Cavity / Q000166:cytology; D011651:Pulmonary Artery / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000166:cytology
D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger; D000804:Angiotensin II