An auxiliary factor of mammalian multi-aminoacyltRNA synthetases, p43, is thought to be a precursor of endothelial monocyte-activating polypeptide II (EMAP II) that triggers proinflammation in leukocytes and macrophages. In the present work, however, we have shown that p43 itself is specifically secreted from intact mammalian cells, while EMAP II is released only when the cells are disrupted. Secretion of p43 was also observed when its expression was increased. These results suggest that p43 itself should be a real cytokine secreted by an active mechanism. To determine the cytokine activity and active domain of p43, we investigated tumor necrosis factor (TNF) and interleukin-8 (IL-8) production from human monocytic THP-1 cells treated with various p43 deletion mutants. The full length of p43 showed higher cytokine activity than EMAP II, further supporting p43 as the active cytokine. p43 was also shown to activate MAPKs and NFB, and to induce cytokines and chemokines such as TNF, IL-8, MCP-1, MIP-1␣, MIP-1␤, MIP-2␣, IL-1␤, and RANTES. Interestingly, the high level of p43 was observed in the foam cells of atherosclerotic lesions. Therefore, p43 could be a novel mediator of atherosclerosis development as well as other inflammation-related diseases.

Abstract:The maintenance of balance between nitric oxide (NO) and the superoxide anion is required for proper functioning of the endothelium. To investigate the relationship between genetic factors associated with endothelial function and the development of coronary artery disease (CAD), endothelial nitric oxide synthase (ecNOS) gene a/b polymorphism and NADH/NADPH oxidase p22 phox gene C242T polymorphism were examined in 305 Korean male CAD patients and 215 healthy male control subjects. The ␤-fibrinogen gene H1/H2 polymorphism was also analyzed. Both ecNOS a/b and p22 phox C242T polymorphisms were found to be associated with the development of CAD in the study population (p = 0.020 and 0.011, respectively). When the association was analyzed by age, statistical significance was retained only in those Ͻ51 years (p = 0.021 and 0.025 for the a/b and the C242T polymorphism, respectively) and not in those Ͼ51 years of age (p =0.155 and 0.278 respectively). However, the distribution of the ␤-fibrinogen H1/H2 genotypes was not found to be associated with the development of CAD in either the Յ50 (p = 0.611) or Ͼ50 groups (p = 0.188). The ecNOS gene a/b polymorphism and the NADH/NADPH oxidase p22 phox gene C242T polymorphism were found to be significantly associated with the development of CAD in Korean male patients less than 51 years old.

BackgroundInflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the involvement of various immune cells in the pathogenesis of atherosclerosis.MethodsWe investigated the presence of foam cells, lymphocytes and killer cells in 11 atherosclerotic plaque specimens removed from Korean patients who underwent carotid endoarterectomy. Atherosclerotic plaques were analyzed by immunohistochemistry using monoclonal antibody specific to foam cells (anti-CD68), pan-T cells (anti-CD3), helper-T cells (anti-CD4), cytotoxic T cells (anti-CD8), granular component of killer cells (anti-TIA-1) and pan-B cells (anti-CD20).ResultsAnalysis revealed a general infiltration of immune cells not only in atherosclerotic plaques but also in the vascular wall adjacent to the plaque. Heavy infiltration of CD68+ macrophage was observed in all cases. In addition, significant infiltration of CD3+ T-lymphocytes was observed in all cases, while CD20+ B-cells were observed in only a few cases. Majority of the CD3+ cells was found to be CD4+ helper-T cells. CD8+ cytotoxic T cells and TIA-1+ cells were less prominent.ConclusionAnalysis of the human atherosclerotic plaques suggested that helper-T cells and foam cells had a major role in the plaque development.