[Analysis of changes in percentage of phenotype CD4 + CD45RA + and CD4+ CD45RO + in peripheral blood and effect of immunomodulation in aged male patients with chronic cardiac insufficiency].

OBJECTIVE: Autoimmunity participates in chronic heart failure (CCI), it is CD4+ T lymphocytes that mainly induces myocardial infiltration and the progression of the disease. The purpose of this research is to assess changes of CD4+, CD8+ T lymphocyte subset, and phenotype of primary T cell (CD4+ CD45RA+) and memory T cells (CD4+ CD45RO+) in peripheral blood in aged male patients with CCI. And to investigate the immunomodulatory effects on subsets of CD4+, CD8+ and phenotype of CD4+ CD45RA+ and CD4+ CD45RO+ and the possible therapeutic mechanism. METHODS: The participant were 155 aged men among whom 94 cases were diagnosed as CCI and heart function of the rest 41 cases were normal. All patients underwent echocardiography examination and were collected peripheral blood before and after treatment. Serum N terminal pro-brain natriuretic peptide (NT-proBNP) levels were detected by heterogeneous immunoassay. Serum C reactive protein (CRP) were measured by immunoturbidimetry assay. T lymphocytes in peripheral blood were separated and determined distribution of CD4+, CD8+, CD4+ CD45RA+, CD4+ CD45RO+ using flow cytometry. Participants were divided into 3 groups: the CCI intervention group, who received regular therapy and thymopentin (20 mg intramuscular injection, once every other day for 3 month; n = 60) , the CCI control group, who received regular therapy (n = 54) and 41 healthy individual older than 57 years of age, who served as normal controls. RESULTS: Compared with the control group, left ventricular ejection fraction (LVEF) and CD4+ CD45RO+ levels decreased, left ventricular end diastolic diameter (LVEDD), NT-proBNP, CRP, CD4+, CD4+ CD45RA+, CD4+/CD8+, CD4+ CD45RA+/CD4+ CD45RO+ levels were obviously higher in CCI group. Distribution of CD8+ was not significantly changed. The level of NT-proBNP, CRP, CD4+/CD8+, CD4+ CD45RA+/CD4+ CD45 RO+ was negatively correlated with LVEF. LVEF could be much improved via decreasing distribution of CD4+/CD8+, CD4+ CD45RA+/CD4+ CD45RO in CCI intervention group than in CCI control group. CONCLUSION: The changes of CD4+/CD8+ and CD4+ CD45RA+/CD4+ CD45RO+ suggest that CD4+ T lymphocyte subset and its phenotype play an important role in the process of CCI. The regulation of CD4+ T lymphocyte and its phenotype may be one of the strategy in the treatment of CCI.

[Analysis of the early and late gene expression of lipopolysaccharide activated macrophages by cDNA microarray].

OBJECTIVE: To study the early and late changes in mRNA expression in macrophages in response to lipopolysaccharide (LPS) with a cDNA microarray approach using the Clontech Atlas microarray. METHODS: mRNA was isolated from unstimulated control and LPS stimulated murine peritoneal macrophages at 2 hours and 24 hours poststimulation, converted to (33)P radiolabeled cDNA, and hybridized to mouse array membranes. RESULTS: In macrophages being stimulated for 2 hours, 69 out of 1 176 genes were found to differ by over 3-fold compared with the control. Among them 44 genes were up-regulated and 25 genes were down-regulated. In macrophages stimulated for 24 hours, 11 genes were up-regulated and 26 genes were down-regulated compared with the control. Only 8 genes were identified both at 2 hours and at 24 hours poststimulation. The expressions of many genes encoding transcription factor, cytokines, cell signaling modulators and apoptosis associated proteins were found to have changed. Some genes that were not previously linked to this model, such as bric-a-brac (BTB) and cap-n-collar(CNC) homology 1(BACH1), early growth response protein 2 (EGR2), E47 interaction protein 1 (EIP1), Ngfi-A binding protein 2 (NAB2), myeloblastosis oncogene-like protein (MYBL2), neurofibromatosis 1 (NF1), ciliarry neurotropic factor (CNTF) and semaphorin 4A (Sema4A). CONCLUSION: This study has allowed us to identify genes that may potentially be regulated by LPS at early and late phase in macrophages. These may contribute to better understanding of the mechanism underlying LPS or bacteria induced inflammatory and immune response following infection and trauma.