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Decrease in Circulating Myeloid Dendritic Cell Precursors in Coronary Artery Disease

Atilla Yilmaz, MD^_*,_*, Jana Weber^_*, Iwona Cicha, PhD^_*, Christian Stumpf, MD^_*, Michael Klein, MD, Dieter Raithel, MD, Werner G. Daniel, MD^_* and Christoph D. Garlichs, MD^_*

^_* Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany
Department of Vascular Surgery, Clinic Nuremberg, Nuremberg, Germany

View larger version (28K): [in a new window]   Figure 1 Gating strategy used for the identification of circulating myeloid dendritic cells and plasmacytoid dendritic cell precursors in peripheral blood by flow cytometry. R1 = gating of peripheral blood mononuclear cells according to their forward and side scatter. R2 = exclusion of granulocytes by side scatter, B lymphocytes by CD19-staining, monocytes by CD14-staining, and dead cells by propidium iodide-staining. R3a and R3b = detection of circulating mDC and pDC precursor as the result of their specific BDCA-1 and BDCA-2 staining, respectively.

View larger version (26K): [in a new window]   Figure 2 Relative and absolute frequency of circulating myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) precursors in patients with stable angina pectoris (SAP, n = 20), with unstable angina pectoris (UAP, n = 19), and acute myocardial infarction (AMI, n = 17) compared with healthy controls (CTL, n = 19). Circulating mDC (A) and pDC (B) precursors shown as a percentage of peripheral blood mononuclear cells (% of PBMC). Circulating mDC (C) and pDC (D) precursors shown as cells per microliter (cells/µl). Graphs show median (line inside box), 25th and 75th percentile (upper and lower boundary of box), and 10th and 90th percentile (whiskers outside box); ns = not significant relative to the control group.

View larger version (12K): [in a new window]   Figure 3 Course of the serum levels of high-sensitivity C-reactive protein and interleukin (IL)-6 (A), circulating myeloid dendritic cell (mDC; B), and plasmacytoid dendritic cell (pDC; C) precursors in patients with acute myocardial infarction (AMI) during the first 24 h (<1 day) and at follow-up after one week (7 days); ns = not significant.

View larger version (27K): [in a new window]   Figure 4 Association of circulating dendritic cell (DC) precursors with inflammatory and atherogenic markers. A significant inverse correlation was observed between the percentage of circulating myeloid dendritic cell (mDC) precursors and serum level of high-sensitivity C-reactive protein (A) or interleukin (IL)-6 (B). There was a lack of any correlation between pDC and hsCRP (C) or IL-6 (D). Linear presentation is shown of mDC or pDC on y-axis and logarithmic presentation of hsCRP and IL-6 on x-axis. ns = not significant.

View larger version (105K): [in a new window]   Figure 5 Immunohistochemical stainings of myeloid dendritic cell (mDC) precursors (BDCA-1), plasmacytoid dendritic cell (pDC) precursors (BDCA-2), tissue-resident DC (fascin), and the DC-specific chemokine MIP-3 in the plaque shoulder (PS) and in the lipid core (LC) of carotid plaques (magnification, x150). (A) Representative example of an atherosclerotic plaque with stable morphology (thick fibrous cap, small lipid core) of an asymptomatic patient. (B) Representative example of an atherosclerotic plaque with a vulnerable morphology (thin fibrous cap, huge lipid core) of a patient with a transient ischemic attack (TIA). Note the remarkably higher frequency of mDC, tissue-resident DC, and MIP-3 in the vulnerable plaque of the patient with TIA compared with the stable plaque of the asymptomatic patient. Only few pDC precursors were observed in both types of plaques.

View larger version (26K): [in a new window]   Figure 6 Histographic presentation of the frequency of myeloid dendritic cell (mDC) precursors (BDCA-1), plasmacytoid dendritic cell (pDC) precursors (BDCA-2), tissue-resident DC (fascin), or MIP-3 (cells/0.25 mm2) in atherosclerotic plaques with stable or vulnerable morphology. Significant association of the number of mDC precursors (A), tissue-resident DC (C), or MIP-3 (D) with plaque vulnerability. No significant association between pDC number and plaque morphology was detected (B).