Mediators of neutrophil recruitment in human abdominal aortic aneurysms.
OBJECTIVE
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.


RESULTS
Conditioned media from luminal, intermediate, and abluminal layers of 29 human ILTs were analysed for neutrophil markers [elastase/alpha1-antitrypsin and MMP9/NGAL complexes, myeloperoxidase (MPO), 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 analysed in vitro. 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 released time dependently 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 CXCR2.


CONCLUSIONS
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.
Houard
Xavier
X
INSERM U698, Cardiovascular Haematology, Bio-Engineering and Remodelings, Paris 7 Denis Diderot University, Bichat-Claude Bernard Hospital, 46 rue Henri Huchard, F-75877 Paris Cedex 18, France.
Touat
Ziad
Z
Ollivier
Véronique
V
Louedec
Liliane
L
Philippe
Monique
M
Sebbag
Uriel
U
Meilhac
Olivier
O
Rossignol
Patrick
P
Michel
Jean-Baptiste
JB
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration; D010978:Platelet Factor 4 / Q000378:metabolism*
D015415:Biomarkers; D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D010978:Platelet Factor 4