Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

BACKGROUND: Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. MATERIALS AND METHODS: Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. RESULTS: Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. CONCLUSION: The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs.

Establishment of a Macrophage-activating Factor Assay System Using the Human Monocytic Cell Line THP-1.

BACKGROUND: As the mechanism of macrophage activation is not well-understood, standardization of an assay system for measuring phagocytic activities of macrophages will be useful for research on macrophages. Previously, we established a novel standardized macrophage-activating factor (MAF) assay system using U937. MATERIALS AND METHODS: Using the human monocytic cell line THP-1, another standardized MAF assay system was established. Characteristic gene expression of U937- and THP-1-derived macrophages was compared by gene expression microarray analysis. RESULTS: Both U937- and THP-1-derived macrophages showed obvious phagocytic activities with unique characteristics and, therefore, could not be assigned to a single sub-type. CONCLUSION: Activation of macrophages is an intricate cellular process. Comparison of our two novel assay systems provides new insights into macrophage activation mechanisms.

Relations of blood pressure to angiotensinogen gene T174M polymorphism and alcohol intake.

To clarify the interactive effects of alcohol intake and angiotensinogen gene codon 174 (T174M) polymorphisms on blood pressure in Japanese male workers. On the basis of data from health examinations, nutrition survey and T174M genotype analysis conducted for 185 Japanese male workers at 2000, the prevalence of high-normal blood pressure (HNBP) and hypertension were compared between the four subgroups crossed by two T174M genotype categories ('TT' type, and 'TM or MM' type) and two alcohol intake categories (less than 13.7 g per day, and 13.7 g or more per day). Furthermore, for 95 subjects who had been normotensive at 1998 among them, risk of development into HNBP or hypertension at 2000 were compared across the four subgroups. The findings showed that the HNBP prevalence adjusted for age, body mass index, smoking habits and sodium intake in 2000 was significantly (p=0.03) greater in 'TM or MM' type (57.9%) than in 'TT' type (24.9%) in subjects with 13.7 g or more of daily alcohol intake, whereas no difference in this parameter was found between the two genotypes in those with less than 13.7 g of daily alcohol intake (18.2% and 18.3%, respectively). The risk for development into HNBP at 2000 was also greatest in 'TM or MM' type with 13.7 g or more of daily alcohol intake among the four subgroups, although there were not significant differences between the four subgroups. The prevalence of hypertension or development risk for hypertension did not significantly differ between the four subgroups. Therefore, it can be seen that alcohol drinking might be specifically associated with the HNBP in M allele carriers of angiotensinogen gene T174M polymorphism.

Association of the longevity-associated mitochondrial DNA 5178 A/C polymorphism with serum protein fraction levels in healthy Japanese women.

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism was reported to be associated with longevity and susceptibility to adult-onset diseases in Japanese. To examine whether mt5178 A/C genotypes are associated with serum protein fraction profiles, we genotyped 461 healthy Japanese individuals, and studied the relationship of mt5178 A/C genotypes to both proportion and levels of serum protein fraction. The mt5178 A/C was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The alpha-1, alpha-2, and beta globulin proportions in females carrying mt5178A were significantly higher than those in females carrying mt5178C (P=0.002, 0.006, and 0.008, respectively). Moreover, the alpha-1, alpha-2, and beta globulin levels in females carrying mt5178A were significantly higher than those in females carrying mt5178C (P=0.001, 0.002, 0.018, respectively). This difference in globulin fraction level between the two genotypes was more evident in premenopausal females than in postmenopausal females. However, no such difference was found in males. These results provide the first evidence that the mt5178 A/C polymorphism may influence the serum protein fraction levels of the healthy Japanese women.