Leukocytes, platelets, and endothelial cells appear to co-activate and interact in areas of vascular injury following severe insult. Leukocyte adhesion to endothelium, a pivotal event in the host defense mechanism and repair of tissue damage, has been shown to induce vascular and tissue injury in sepsis. Microparticles (MPs) have been recently detected as vesicles that are shed from various kinds of activated cells, and they have specific membrane components. MPs originated from polymorphonuclear leukocytes (PMNLs), platelets, and endothelial cells were discovered in vitro by recently developed flow cytometric methods. PMNL-derived MPs have been recently found to be activators of vascular endothelium in vitro. Levels of platelet-derived MPs have been shown to be elevated in various conditions including unstable angina, diabetes, and post cardiac surgery. Endothelial cell-derived MPs are increased in patients with a coagulation abnormality characterized by the presence of lupus anticoagulant and in patients with acute coronary syndrome.
These MPs are considered to activate other cells and to perhaps play a novel role in the pathogenesis of various diseases. The precise role of these MPs, however, has not been clarified in patients with sepsis. We developed a flow cytometric method for detecting these MP formation and quantitatively evaluating them in patients with sepsis. The production of each MP was significantly increased and the interaction between these MPs and other inflammatory cells was enhanced in the patients.
This review will provide an overview of our current understanding of PMNL-, platelet- and endothelial cellderived MPs and their orchestration in sepsis patients.

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Atherosclerosis is responsible for more than half of all deaths in western countries. Numerous studies have reported that accumulation of smooth muscle cells (SMCs) plays a principal role in atherogenesis, post-angioplasty restenosis and transplantation-associated vasculopathy. Although much effort has been devoted targeting migration and proliferation of medial smooth muscle cells, no effective therapy to prevent occlusive vascular remodeling has been established. Recently, we suggested that bone marrow-derived precursors can give rise to vascular cells that contribute to repair, remodeling, and lesion formation of arterial wall under certain circumstances. This article overviews recent findings on vascular precursors and describes potential therapeutic strategies for vascular diseases, targeting mobilization, homing, differentiation and proliferation of circulating progenitor cells.

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Prostanoids including prostaglandins (PGs) and thromboxanes (TX) are a group of lipid mediators produced from membrane lipid in response to various stimuli. While the roles of prostanoids in acute inflammatory responses have been well defined, it is generally believed that prostanoids don't play significant roles in the immune response. This is partly because non-steroidal anti-inflammatory drugs that inhibit all prostanoid synthesis have little effects on immune processes in vivo. Prostanoids exert their actions by acting on a family of G-protein-coupled receptors, including PGD receptor, EP1, EP2, EP3 and EP4 subtypes of PGE receptor, PGF receptor, PGI receptor and TX receptor. We generated mice deficient in each of these prostanoid receptors, and examined their roles under various pathological conditions. These studies have revealed that prostanoids works at various levels of immune responses and exert many, often opposing, actions. For example, we found that PGE₂-EP4 signaling facilitates migration and maturation of dendritic cells in contact hypersensitivity, while the same pathway suppresses T cell activation and proliferation in the gut of mice subjected to dextran sodium sulfate-induced colitis, a model of inflammatory bowel disease. These findings suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of certain immunological disorders.

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Autologous cultivated mucosal epithelial cells from a non-ocular surface origin were investigated to determine their possible use in ocular surface reconstruction. An ocular-surface injury was created in one eye of each of the adult albino rabbits used, via lamellar keratectomy. Next, oral mucosal biopsies were taken from these rabbits and then cultivated for 2-3 weeks on denuded amniotic membrane. The cultivated oral epithelial sheets were examined by electron microscopy (EM) and immunohistochemically labeled for several keratins. EM revealed that the epithelial cells were very similar in appearance to those of in vivo normal corneal epithelium. It also showed that they had numerous desmosomal junctions and were strongly attached to a basement membrane with hemi-desmosomes. Immunohistochemistry confirmed the presence of non-keratinized, stratified keratins 4/13 and cornea-specific keratin 3. All of the corneas that were transplanted with the autologous cultivated oral epithelial sheets were clear and epithelialized 10 days after transplantation. From these results, we conclude that the autologous transplantation of cultivated oral epithelium is a feasible procedure for ocular surface reconstruction.

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Chronic granulomatous disease (CGD) is characterized by the failure of phagocytes to kill certain bacteria and fungi. This is caused by deficiencies in one of the components of NADPH oxidase, a superoxide-producing enzyme in phagocytic leukocytes. In some cases with missense mutations in the p67^phox gene, mRNA for p67^phox is present in normal amounts; however, p67^phox protein is missing, suggesting that the missense p67^phox protein is labile in the cytosol of phagocytic cells in CGD. In this study, we evaluated the degradation of missense mutants of p67^phox using p67^phox G78E (⁷⁸Gly → Glu) and A128Val (¹²⁸Ala → Val) as target molecules. By incubation with the cytosol factions of human peripheral blood neutrophils and promyelocytic HL-60 cells, G78E and A128V were time-dependently degraded, whereas wild-type p67^phox was not degraded. Importantly, the degradation of missense mutant G78E was completely abolished by inhibitors for serine proteases such as DFP, PMSF and soybean trypsin inhibitor, but was not affected by proteasome inhibitor MG-132 and calpain inhibitor ALLN. These observations suggest that missense mutants of p67^phox are labile and likely to be degraded in CGD by cytosolic serine protease(s) in phagocytic cells, and proteasome and calpain are unlikely to be involved in the degradation.

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There has been considerable interest in traditional Chinese herbal therapy as a novel treatment for atopic dermatitis (AD). To investigate the efficacy and safety of formulas of traditional Chinese herbal medicine, Kujin-Plus, 94 AD patients received oral administration of the formula, Kujin-Plus I, containing 10 herbs, combined with a lotion, Kujin-Plus II, containing 7 herbs, and an ointment, Kujin-Plus III, containing 8 herbs as an open trial. The severity of the disease (clinical score; 0-4) and the severity of pruritus (pruritus score; 0-4) were judged by standardized scores. Both scores were significantly improved at the end of the treatment (p < 0.01;nonparametric test). The blood eosinophil ratio and serum IgE levels were high in AD patients and they were significantly reduced at the end of the treatment (p < 0.001). Of 94 AD patients with traditional Chinese herbal therapy, 32 were markedly improved, 59 were improved, 3 were slightly improved and none was ineffective. There was no remarkable evidence of renal or hepatic toxicity or another severe adverse effects. Thus, the present study confirmed that this herbal treatment is clinically efficacious on AD with a significant reduction in blood eosinophil ratio and serum IgE level.

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