Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients.

Acute ST-elevation myocardial infarction (STEMI) leads to myocardial injury or necrosis, and M1 macrophages play an important role in the inflammatory response. Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are capable of modulating macrophage plasticity, principally due to their immunoregulatory capacity. In the present study, we analyzed the capacity of MSCs to modulate macrophages derived from monocytes from patients with STEMI. We analyzed the circulating levels of cytokines associated with M1 and M2 macrophages in patients with STEMI, and the levels of cytokines associated with M1 macrophages were significantly higher in patients with STEMI than in controls. BM-MSCs facilitate the generation of M1 and M2 macrophages. M1 macrophages cocultured with MSCs did not have decreased M1 marker expression, but these macrophages had an increased expression of markers of the M2 macrophage phenotype (CD14, CD163 and CD206) and IL-10 and IL-1Ra signaling-induced regulatory T cells (Tregs). M2 macrophages from patients with STEMI had an increased expression of M2 phenotypic markers in coculture with BM-MSCs, as well as an increased secretion of anti-inflammatory cytokines and an increased generation of Tregs. The findings in this study indicate that BM-MSCs have the ability to modulate the M1 macrophage response, which could improve cardiac tissue damage in patients with STEMI.

Effect of Interleukin-17 in the Activation of Monocyte Subsets in Patients with ST-Segment Elevation Myocardial Infarction.

Interleukin- (IL-) 17 is increased in acute myocardial infarction (AMI) and plays a key role in inflammatory diseases through its involvement in the activation of leukocytes. Here, we describe for the first time the effect of IL-17 in the migration and activation of monocyte subsets in patients during ST-segment elevation myocardial infarction (STEMI) and post-STEMI. We analyzed the circulating levels of IL-17 in patient plasma. A gradual increase in IL-17 was found in STEMI and post-STEMI patients. Additionally, IL-17 had a powerful effect on the recruitment of CD14++CD16+/CD14+CD16++ monocytes derived from patients post-STEMI compared with the monocytes from patients with STEMI, suggesting that IL-17 recruits monocytes with inflammatory activity post-STEMI. Furthermore, IL-17 increased the expression of TLR4 on CD14 + CD16 - and CD14++CD16+/CD14+CD16++ monocytes post-STEMI and might enhance the response to danger-associated molecular patterns post-STEMI. Moreover, IL-17 induced secretion of IL-6 from CD14++CD16- and CD14++CD16+/CD14+CD16++ monocytes both in STEMI and in post-STEMI, which indicates that IL-17 has an effect on the secretion of proinflammatory cytokines from monocytes during STEMI and post-STEMI. Overall, we demonstrate that in STEMI and post-STEMI, IL-17 is increased and induces the migration and activation of monocyte subsets, possibly contributing to the inflammatory response through TLR4 and IL-6 secretion.

Haplotype block 1 variant (HB-1v) of the NKG2 family of receptors.

The natural killer group 2 (NKG2) family of receptors, encoded within the NK complex gene region (NKC), modulate the cytotoxic activity of NK cells. Two haplotype blocks throughout the NKC, hb-1 and hb-2 have been associated with different levels of overall natural cytotoxicity. Here, we evaluated allelic and genotype frequencies at rs1049174, rs2617160, rs2617170, rs2617171, rs1983526 (hb-1 haplotype), and rs2255336 and rs2246809 (hb-2 haplotype) in 928 subjects examined from Mexico City. The most frequent alleles and genotypes were as follows: C, CG to rs1049174; G, GG to rs2255336; T, AT to rs2617160; G, GG to rs2246809; C, CT to rs2617170; G, CG to rs2617171; and G, CG to rs1983526. Linkage disequilibrium analysis revealed that rs1049174, rs2617160, rs2617170, and rs2617171 constituted the haplotype block-1 variant (hb-1v) (r2 ≥ 0.89). Two predominant haplotypes of hb-1v were identified based on the allele content and included CTCG and GATC. This study is the first to evaluate the allelic and genotype frequency distribution of rs1049174, rs2255336, rs2617160, rs2246809, rs2617170, rs2617171, and rs1983526 in the population of Mexico City.