Abstract 2247: Dynamic Activation Status of Circulating Myeloid Cells During the Very Acute Phase of ST-Segment Elevation Myocardial Infarction
Background: Although coagulation and inflammation closely interact in the progression of atherosclerosis, much remains to be learned on the critical pathways that could advantageously be blocked in acute coronary syndromes. In this study we characterized the status of activation of myeloid cells during the very acute phase of STEMI.
Method: Whole blood samples were collected from 39 consecutive patients with STEMI admitted within 2 hours of onset of symptoms, before any new drug administration. Flowcytometry analyses were performed in the basal state and after addition of a thrombin receptor agonist peptide (TRAP, 10μM) and of phorbol myristate acetate (PMA, 240μg/L) for more selective activation of platelets and myeloid cells respectively. MO-1-FITC was used to quantify MAC1 (CD11b/CD18) expression on monocytes and neutrophils (PMN) as assessed by mean fluorescence intensity, and anti-TF-FITC to quantify tissue factor (TF) expression on these cells assessed by the percentages of FITC-positive cells. Control studies were obtained in 40 individuals (C), 20 with no disease and 20 with stable angina; as data of these two groups considered separately or together were very similar, the pooled data were used for statistical comparison with STEMI.
Results: White cell counts at admission were higher in STEMI (11±3.4) than in C (7±1.59, P<0.01), but MAC1 and TF expression on monocytes or PMN were no different between groups. In controls, TRAP increased MAC-1 expression from 4.0±1 to 9.4±2 on monocytes and from 2.3±0.9 to 7.4±1.9 on PMN; PMA increased TF expression from 6.1±7 to 38.7±16.4 on monocytes and from 3.3±3.2 to 6.3±6.2 on PMN (all p<0.01). In STEMI compared to C, TRAP-induced MAC-1 expression increased by 21% to 11.4±2.7 on monocytes and by 30% to 9.6±2.1 on PMN, and PMA-induced TF expression by 40% to 53.9±17.7 and 50% to 9.3±8.6 respectively (all p<0.01).
Conclusion: The first few hours of MI are associated with a priming of monocytes and PMN that makes them hyper-responsive to the agonist effect of a thrombin receptor agonist peptide and of PMA. Any additional leukocyte activation can therefore result in a large production of TF mainly by monocytes, but also by PMN. Dynamic studies of leukocytes may be more informative than static studies in very acute situations.