title: Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines.
abstract: 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.
authors.affiliation: Department of Pharmacology,Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Yafa Naim Abu
authors.initials: YN
authors.lastname: Nabah
authors.forename: Teresa
authors.initials: T
authors.lastname: Mateo
authors.forename: Rossana
authors.initials: R
authors.lastname: Estellés
authors.forename: Manuel
authors.initials: M
authors.lastname: Mata
authors.forename: John
authors.initials: J
authors.lastname: Zagorski
authors.forename: Henry
authors.initials: H
authors.lastname: Sarau
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Morcillo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jose
authors.forename: Maria-Jesus
authors.initials: MJ
authors.lastname: Sanz
mesh_terms: 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
chemical_list: D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger; D000804:Angiotensin II