Stadien-abhängiger Nachweis von CD14+- und CD16+-Zellen im humanen Herz- und Milzgewebe nach Myokardinfarkt: Eine post-mortem-Analyse

Stadien-abhängiger Nachweis von CD14+- und CD16+-Zellen im humanen Herz- und Milzgewebe nach Myokardinfarkt: Eine post-mortem-Analyse

Stage-dependent detection of CD14+ and CD16+ immune cells in human heart tissue after myocardial infarction: A post-mortem analysis

Magdalena Schlegel

Doctoral thesis

Date of Examination: 2014-07-23

Date of issue: 2014-07-02

Advisor: Schäfer, Katrin Prof. Dr.

Referee: Schön, Margarete Prof. Dr.

Referee: Dressel, Ralf Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0022-5F05-E

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Abstract

English

Monocytes play an important role in cardiovascular wound healing processes. Human monocytes can be classified into two subsets based on the expression of CD14 and CD16. Here, the temporal and spatial distribution of CD14⁺ and CD16⁺ cells after myocardial infarction (MI) in human heart and spleen tissue was examined and correlated with markers of cardiac repair. Heart samples obtained at autopsy were histologically classified into acute (AMI; n = 11), subacute (SAMI; n = 10) and old (OMI; n = 16) MI, or control myocardium (CONTR; n = 8). Histochemical analyses of heart tissue revealed an increase of CD14⁺ and CD16⁺ cells in subjects with SAMI. Regarding a MI-associated release of monocytes from spleen reservoirs, a non-significant reduction of splenic CD14⁺ and CD16⁺ cells was detected in subjects with AMI with an increased number of CD14⁺, CD16⁺ and Ki67⁺ cells in SAMI. The hypoxia indicator carbonic anhydrase IX was predominantly expressed in AMI (p < 0.01 vs. OMI and CONTR) and SAMI (p < 0.05 vs. OMI and CONTR). The number of capillaries was increased in AMI (p<0,05 vs. OMI), showing that hypoxia is a strong trigger off angiogenesis. Marked fibrosis could be observed in OMI (p<0,001 vs. CONTR). The adhesion molecule CD56 was also strongly expressed in OMI (p < 0.01 vs. CONTR) and found to correlate with fibrosis (p < 0.001). The monocyte chemoattractrant osteopontin was more highly expressed in hearts of SAMI patients (p < 0.01 vs. CONTR). KLF4⁺ cells were also increased in SAMI (p<0,001 vs. OMI), which could indicate a switch between the inflammatory and reparative phase of MI by influencing the polarization of monocytes. In conclusion, disease stage-specific alterations in CD14⁺ and CD16⁺ cells in human heart may contribute to cardiac repair processes following MI.

Keywords: Monocytes; CD14; CD16; Myocardial infarction; Osteopontin; KLF4