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Background Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium. Methods Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining. Results The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction. Conclusion These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium.

Background Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms. Materials and methods/results CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFNgamma), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and FcgammaRIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions. Conclusions We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response.

Background Systemic inflammation and apoptosis-specific immune activation play a major role in acute coronary syndromes (ACS) including acute myocardial infarction (AMI). The role of systemic and coronary obtained inflammatory plasma protein interleukin-1β precursor (IL-1βp), IL-1β-converting enzyme (ICE) and the apoptosis-specific caspase-cleaved cytokeratin-18 (ccCK-18) are not known in ACS. Materials and methods Plasma samples were obtained from stable angina (SA, n = 34), unstable angina (UA, n = 37) and patients with AMI (n = 39). Coronary blood was acquired by means of thrombectomy devices (X-sizer) in AMI patients. IL-1βp, ICE and ccCK-18 were determined by enzyme-linked immunosorbent assay (ELISA). Group comparisons were evaluated by parametric Tukey test. Multivariate logistic regression analysis was performed to determine predictive values of IL-1βp, ICE and ccCK-18 as compared to creatine kinase (CK) and troponin T (TnT) in order to relate these markers with the occurrence of myocardial damage. Results IL-1βp, ICE and ccCK-18 were identified to be significantly altered in the peripheral blood of patients suffering from AMI as compared to SA and UA. ROC curves were plotted and revealed that ccCK-18 is a novel sensitive marker for the detection of myocardial damage as compared to TnT or CK. (AUC ccCK-18 0·925, TnT AUC 0·62 and CK AUC 0·858.) Moreover, ICE and ccCK-18 were significantly increased at the site of coronary occlusion as compared to peripheral blood samples in AMI patients (both P

Background Acute coronary syndrome is related to increased circulatory concentration of soluble apoptosis specific caspase-cleaved cytokeratin-18 (ccCK-18). Potential cardiac sources of this intermediate filament derivative have not been investigated to date. Materials and methods Paraffin embedded tissue of normal myocardium, and chronically damaged samples of ischaemic, congestive and hypertrophic cardiomyopathy were analysed by histology and by CK-8, CK-18, ccCK-18 immunohistochemistry (each group, n = 15). Antibody specificity of the ccCK-18 antibody M30 was checked by immunoblotting on lysed myocardium and enriched myocardial lysosomes. Results ccCK-18 and CK-18 but not CK-8 were present in all forms of cardiomyopathy, most prominently in ischaemic cardiomyopathy while only traces were detectable immunohistochemically in normal myocardium. Weak CK-18 and strong ccCK-18 staining co-localized to lysosomes with cardiac age pigment lipofuscin. Weak staining of CK-18 was detected in the cytoplasm of coronary endothelia. Conclusion Our study reveals that cardiac lipofuscin-laden lysosomes contain ccCK-18, a marker of apoptosis and its precursor CK-18. This ccCK-18 pool might contribute to increased systemic levels of ccCK-18 in acute coronary syndrome thus monitoring myocardial damage.