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Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 5, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp048
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

Mediators of neutrophil recruitment in human abdominal aortic aneurysms

Xavier Houard*, Ziad Touat*, Véronique Ollivier*, Liliane Louedec*, Monique Philippe*, Uriel Sebbag#, Olivier Meilhac*, Patrick Rossignol§ and Jean-Baptiste Michel*,$

* INSERM U698, Paris 7 Denis Diderot University, Cardiovascular Haematology, Bio-Engineering and Remodelings. Bichat-Claude Bernard Hospital, 46 rue Henri Huchard, F-75877 Paris Cedex 18. France
# Centre Cardiologique du Nord. 32-36 rue des Moulins Gémeaux, F-93207 Saint Denis Cedex. France
§ Centre d'Investigation Clinique de Nancy CIC-P 9501, INSERM, CHU de Nancy, Nancy-University, F-54201 Dommartin-lès-Toul. France

$ Address for correspondence: Jean-Baptiste Michel, MD, PhD., INSERM U698 "Cardiovascular Hematology, Bio-Engineering and Remodelings", Hôpital X. Bichat, 46, rue Henri Huchard, 75877 Paris Cedex 18, France, Tel: 33-1-40-25-86-00, Fax: 33-1-40-25-86-02, Email: jean-baptiste.michel{at}inserm.fr

Aims: Neutrophils/platelet interactions are involved in abdominal aortic aneurysm (AAA). The intraluminal thrombus (ILT) is a human model of platelet/neutrophil interactions. The present study focused on mediators involved in neutrophil recruitment in AAA.

Methods: Conditioned media from luminal, intermediate and abluminal layers of 29 human ILTs were analyzed for neutrophil markers (elastase/{alpha}1-antitrypsin and MMP9/NGAL complexes, myeloperoxidase and {alpha}-defensin peptides), RANTES, platelet factor 4 (PF4) and interleukin-8 (IL-8). Their time-dependent release into serum from clots generated in vitro and their plasma concentrations in AAA patients and controls were determined. Immunohistochemistry for neutrophils, platelets, IL-8, PF4 and RANTES on AAA sections was performed; and molecules involved in ILT neutrophil chemotactic function were analyzed in vitro.

Results: Neutrophils and platelets colocalized in the luminal layer of the thrombus. Consistently, neutrophil markers and platelet-derived RANTES and PF4 were released predominantly by the luminal thrombus pole where their concentrations were significantly correlated. The luminal ILT layer was also the main source of IL-8, whose immunostaining colocalized with neutrophils. All were also time-dependently released from clots and were increased in plasma of AAA patients. Luminal ILT layers displayed potent neutrophil chemotactic activity in vitro, which was inhibited by RANTES- and IL-8-blocking antibodies as well as by reparixin, an antagonist of the IL-8 receptors CXCR1 and CXCR-2.

Conclusion: Taken together, these results suggest that platelet-derived RANTES and neutrophil-derived IL-8 are involved in attracting neutrophils to the luminal layer of AAA ILT.

KEYWORDS intraluminal thrombus; interleukin-8; RANTES; PF4; MMP9/NGAL; MPO; elastase/{alpha}1-antitrypsin; {alpha}-defensins

Time for primary review: 34 Days


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