title: Recruitment of circulating dendritic cell precursors into the infarcted myocardium and pro-inflammatory response in acute myocardial infarction.
abstract: DC (dendritic cells) play an important role in the immune system. They invade peripheral tissues to detect harmful antigens, inducing a local immune response. Studies suggest that DCPs (dendritic cell precursors) might be reduced in AMI (acute myocardial infarction); however, the reason for their reduction is unknown yet. In the present study, circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs), tDCPs (total DCPs) and serum levels of TNFα (tumour necrosis factor α), IL (interleukin)-2, -4, -5, -6, -10 and -12 were analysed by flow cytometry in blood of patients with NSTEMI [non-STEMI (ST-segment elevation myocardial infarction)] (n=44) and STEMI (n=34) compared with controls with excluded CAD (coronary artery disease) (n=45). Post-mortem myocardial specimens of patients with AMI (n=12) and healthy myocardium of accident victims (n=10) were immunostained for mDCs (myeloid dendritic cells) T-cells and macrophages. Compared with controls, in patients with AMI a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.0001). The extent of the decrease was higher in STEMI than NSTEMI patients. Serum levels were significantly higher in patients with AMI compared with controls for IL-6, -10, -12 and TNFα (each P<0.03). Immunostaining revealed significantly higher number of DCs, T-cells and macrophages (each P<0.002) in infarcted than control myocardium. We show that circulating DCPs are significantly reduced in AMI, with a pronounced reduction in STEMI patients. This was accompanied by a significant increase of inflammatory serum cytokines in patients with AMI. Immunohistochemical analysis unravelled that the reduction of circulating DCPs might be due to recruitment into the infarcted myocardium.
authors.affiliation: Department of Internal Medicine I, Division of Cardiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany. daniel.kretzschmar@med.uni-jena.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Kretzschmar
authors.forename: Stefan
authors.initials: S
authors.lastname: Betge
authors.forename: Alexander
authors.initials: A
authors.lastname: Windisch
authors.forename: Rudin
authors.initials: R
authors.lastname: Pistulli
authors.forename: Ilonka
authors.initials: I
authors.lastname: Rohm
authors.forename: Michael
authors.initials: M
authors.lastname: Fritzenwanger
authors.forename: Christian
authors.initials: C
authors.lastname: Jung
authors.forename: Katja
authors.initials: K
authors.lastname: Schubert
authors.forename: Bernhard
authors.initials: B
authors.lastname: Theis
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Drobnik
authors.forename: Gita
authors.initials: G
authors.lastname: Mall
authors.forename: Hans-Reiner
authors.initials: HR
authors.lastname: Figulla
authors.forename: Atilla
authors.initials: A
authors.lastname: Yilmaz
mesh_terms: D000368:Aged; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000473:pathology* / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha