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Aim: Scavenger receptors type I and II (SRBI/II) have dual roles in both atherogenic and antiatherogenic functions through interactions with lipoproteins and their expression in macrophages; how-ever, the distribution and density of SRBI/II-positive macrophages and smooth muscle cells (SMCs) as well as their association with lipid metabolism-related proteins in atherosclerotic intima of the human aorta remain unclear., Methods: Autopsied aortic tissues were double-immunostained with SRBI/BII and smooth muscle actin or macrophage-specific antibodies. The density of SRBI/BII-positive SMCs and macrophages in intimal lesion was measured. They were also immunostained with antibodies against four apolipoproteins, four phospholipase A2s, and CETP., Results: SRBI/II was expressed in both macrophages and SMCs distributed in various intimal lesions. The density of SRBI/II-positive SMCs in intimal lesions significantly decreased with the advance of atherosclerosis, whereas the density of SRBI/II-positive macrophages significantly increased with atherosclerotic development. In addition, functional proteins, such as apolipoproteins, secretory phospholipase A2s, and CETP, were distributed in the intimal stroma around SRBI/II-positive cells in all lesion types., Conclusion: The results indicated that SMCs are involved in lipid metabolism via SRBI/II expression mainly in the early stages of atherosclerosis evolution, and that SRBI/II-positive macrophages are mainly involved in advanced stages.

Secretory phospholipase A2s (sPLA2s) contribute to the hydrolysis of phospholipid. Among them, sPLA2-IIA, -V, and -X have been regarded as enhancers of lipid accumulation in arterial intima. However, the distribution and production of the other types of sPLA2 in human aortic wall remain unclear. Therefore, in this study, the distribution and production of seven types of sPLA2 including IIA, IID, IIE, IIF, III, V, and X in atherosclerosis development in the human aorta were comprehensively examined by immunohistochemistry and in situ hybridization (ISH). The extent of sPLA2s expression increased with atherosclerosis development, but only sPLA2-IIF was never observed in the normal aorta. Double-immunostaining demonstrated that sPLA2-V expression was limited to smooth muscle cells (SMCs), although the other sPLA2s were expressed in both macrophages and SMCs. ISH using sPLA2 cDNAs revealed that the expression pattern of each mRNA was consistent with the results of immunohistochemistry for each corresponding sPLA2. These results indicate that the seven types of sPLA2 are expressed with various patterns in all stages of atherosclerosis development and may play an atherogenic role through degradation of phospholipid.

We studied the associations of lymphatic invasion and lymphatic vessel density around tumors with lymph node (LN) status in renal cell carcinoma (RCC) by immunohistochemical analysis using D2-40 antibody as a lymphatic marker. Surgically removed specimens from 76 cases with RCC, including 16 cases with LN metastasis, were used. Lymphatic vessel density around the tumor increased compared with normal kidneys but was not significant by LN status. Tumor size, tumor cell types, patterns of tumor growth, nuclear grade of tumor cells, venous invasion, lymphatic invasion, and primary tumor stage were predictive factors for LN metastasis. Based on multivariate regression analysis, only lymphatic invasion was an independent risk factor for LN metastasis. The immunohistochemical detection of lymphatics was useful for identifying the lymphatic invasion of RCC, and the presence of lymphatic invasion around RCC was an independent predictive factor for LN metastasis.

To clarify the role of myocardial apoptosis associated with the expression of proinflammatory cytokines in human myocardial infarction (MI), we have analyzed the expression of apoptosis positive for single-stranded DNA (ss-DNA) antibody, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-8 in 147 samples of infarcted myocardial tissue from 65 patients. ss-DNA-positive apoptotic nuclei were found mainly in cardiomyocytes in the border zones and granulation tissue cells in the infarct foci. The ss-DNA index (SI) of cardiomyocytes (average 0.13%) peaked at stage II (established myocardial necrosis), the value being significantly higher than at stages III (macrophage infiltration), IV (granulation formation), and V (scar formation) (P<0.05), whereas the SI of granulation tissue (average 0.08%) at stages III, IV, and V showed no significant differences between the three stages. These results suggest that cardiomyocyte apoptosis in the border zone is responsible for cellular loss in the acute stage of MI, whereas granulation tissue apoptosis may not be involved in the process of ventricular remodeling. TNF-alpha was expressed in cardiomyocytes in the border zones of infarct foci, but no significant positive correlation was found between SI and TNF-alpha index in cardiomyocytes (r=0.08, P = 0.37), suggesting that TNF-alpha does not serve as a direct trigger of cardiomyocyte apoptosis in vivo. The number of IL-8-positive cells peaked at stage II, and IL-8-myeloperoxidase-double-positive neutrophils were frequently detected, indicating that infiltrating neutrophils are the predominant source of IL-8 in the infarcted myocardium. These results suggest that, in human MI, TNF-alpha produced by cardiomyocytes does not play a critical role in their apoptosis, and that IL-8 produced by neutrophils is responsible for the subsequent accumulation and activation of neutrophils, thus increasing the degree of myocardial damage.