P1760Local coronary activation of neutrophils at the site of the culprit lesion in patients with an acute coronary syndrome

Abstract

Background: As observed for other cells of the innate immunity, subpopulations of neutrophils can harbour pro-inflammatory as well as pro-regenerative effects. The individual activation of those sub-populations at the site of an acute vascular occlusion might contribute to the further disease development and complications. Methods: In this pilot study, we studied the expression of relevant receptors (e.g. TLR2 and 4, CXCR4, VEGF receptor 1) on overall neutrophils in blood samples obtained from the site of of the culprit lesion (L) and in blood samples obtained from the radial or femoral artery at the time of catheterization (peripheral site; P) in patients with acute myocardial infarction. In the same samples, we assessed concentrations of cytokines and complement factors associated with neutrophil activation. Results: Neutrophils within the L sample exhibited significantly decreased granularity as compared to neutrophils within the P sample, indicating their local degranulation at the lesion site (n=74). Increased levels of interleukin 10 and macrophage inflammatory protein 1a (MIP-1a, n=74) within L plasma samples support a release of neutrophil-derived cytokines. Interleukin 8, serving as a neutrophil activator in addition to MIP-1a, was also increased in L plasma (n=74). Differential enrichment and activation behaviour was detected in subpopulations of neutrophils, expressing the VEGFR1 as well as the TLR2 (n=21). Conclusions: Our results indicate specific activation and recruitment mechanisms for individual subpopulations of neutrophils in acute coronary occlusion, including the involvement of the VEGFR1 and the TLR2. Further analyses have to determine the role of individual VEGF responsive neutrophil subpopulations versus those activated by damage-asociated molecular patterns via TLR2 in acute vascular occlusion. Our data underline the critical role of the innate immune system, in particular neutrophils, and the heterogeneity of neutrophil subpopulations in acute coronary syndrome.