Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease.
Accumulating evidence support a role of neutrophils in coronary artery disease (CAD). However little is known about the action of neutrophils at a local inflammatory site represented by an atherosclerotic plaque. To gain insight into these issues, we applied a skin blister model that permits analyses of in vivo transmigrated neutrophils. We hypothesised that the chronic inflammation in stable CAD mediates priming of neutrophils that impacts the out-come of neutrophil action at an inflammatory site. Thirteen patients with angiographically verified CAD were eligible for study entry together with 13 age and sex matched controls. Markers of inflammation (IL-6 and CRP), neutrophil activation (IL-8 and MMP-9/NGAL), and functional aspects (CD11b up-regulation and intracellular H(2)O(2) production) of peripheral and in vivo transmigrated neutrophils were studied. Systemic IL-8 and MMP-9/NGAL concentrations were significantly increased in patients indicating a primed state in circulating neutrophils. In vivo transmigrated neutrophils in stable CAD patients had an increased propensity to release MMP-9/NGAL and a reduced capacity to up-regulate CD11b and to produce hydrogen peroxide. These aberrations at the inflammatory site may be a consequence of a primed state of circulating neutrophils and point towards potential mechanisms whereby neutrophils at a local inflammatory site may contribute to the pathogenesis of CAD.
Paulsson
Josefin
J
Department of Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden. Josefin.Paulsson@ki.se <Josefin.Paulsson@ki.se>
Dadfar
Elham
E
Held
Claes
C
Jacobson
Stefan H
SH
Lundahl
Joachim
J
D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D001768:Blister / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis; D002465:Cell Movement; D003324:Coronary Artery Disease / Q000276:immunology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007958:Leukocyte Count; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D018375:Neutrophil Activation / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000097:blood; D016897:Respiratory Burst / Q000502:physiology; D012867:Skin / Q000276:immunology; D015854:Up-Regulation
D000209:Acute-Phase Proteins; D039481:CD11b Antigen; C509295:ITGAM protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9