Efficient engulfment of the intact cell corpse is a critical end point of apoptosis, required to prevent secondary necrosis and inflammation. The presentation of "eat-me" signals on the dying cell is an important part of this process of recognition and engulfment by professional phagocytes. Here, we present evidence that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of this chemotactic factor(s). The putative chemoattractant was identified as the phospholipid, lysophosphatidylcholine. Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2). These data suggest that in addition to eat-me signals, apoptotic cells display attraction signals to ensure the efficient removal of apoptotic cells and prevent postapoptotic necrosis.

OBJECTIVE -The ␣ 2 -Heremans-Schmid glycoprotein (AHSG; fetuin-A in animals) impairs insulin signaling in vitro and in rodents. Whether AHSG is associated with insulin resistance in humans is under investigation. In an animal model of diet-induced obesity that is commonly associated with hepatic steatosis, an increase in Ahsg mRNA expression was observed in the liver. Therefore, we hypothesized that the AHSG plasma protein, which is exclusively secreted by the liver in humans, may not only be associated with insulin resistance but also with fat accumulation in the liver.RESEARCH DESIGN AND METHODS -Data from 106 healthy Caucasians without type 2 diabetes were included in cross-sectional analyses. A subgroup of 47 individuals had data from a longitudinal study. Insulin sensitivity was measured by a euglycemic-hyperinsulinemic clamp, and liver fat was determined by 1 H magnetic resonance spectroscopy.RESULTS -AHSG plasma levels, adjusted for age, sex, and percentage of body fat, were higher in subjects with impaired glucose tolerance compared with subjects with normal glucose tolerance (P ϭ 0.006). AHSG plasma levels were negatively associated with insulin sensitivity (r ϭ Ϫ0.22, P ϭ 0.03) in cross-sectional analyses. Moreover, they were positively associated with liver fat (r ϭ 0.27, P ϭ 0.01). In longitudinal analyses, under weight loss, a decrease in liver fat was accompanied by a decrease in AHSG plasma concentrations. Furthermore, high AHSG levels at baseline predicted less increase in insulin sensitivity (P ϭ 0.02).CONCLUSIONS -We found that high AHSG plasma levels are associated with insulin resistance in humans. Moreover, AHSG plasma levels are elevated in subjects with fat accumulation in the liver. This is consistent with a potential role of AHSG as a link between fatty liver and insulin resistance. Diabetes Care 29:853-857, 2006I nsulin resistance plays a crucial role in the development of type 2 diabetes (1). Multiple mechanisms are thought to be involved in its pathogenesis. Among them, the human ␣ 2 -Heremans-Schmid glycoprotein (AHSG) was found to be important in animals and in in vitro studies. It is an abundant serum protein in mammals. Bovine and murine fetuin-A and pp63 in rats are homologues of AHSG (2,3). In humans, except for the tongue and the placenta, it is exclusively expressed in the liver (4). It is a natural inhibitor of the insulin-stimulated insulin receptor tyrosine kinase (3). Acute injection of human recombinant AHSG inhibi t e d i n s u l i n -s t i m u l a t e d t y r o s i n e phosphorylation of the insulin receptor and insulin receptor substrate-1 in rat liver and skeletal muscle (3). In addition, AHSG knockout mice display improved insulin sensitivity and are resistant to weight gain on a high-fat diet (5).While these data reflect that AHSG is an important candidate among the factors that induce insulin resistance, the role of this protein in the natural history of type 2 diabetes is still unclear (6). Recent reports from genetic studies suggest that single nucleotide polymor...

De novo lymphangiogenesis influences the course of different human diseases as diverse as chronic renal transplant rejection and tumor metastasis. The cellular mechanisms of lymphangiogenesis in human diseases are currently unknown, and could involve division of local preexisting endothelial cells or incorporation of circulating progenitors. We analyzed renal tissues of individuals with gender-mismatched transplants who had transplant rejection and high rates of overall lymphatic endothelial proliferation as well as massive chronic inflammation. Donor-derived cells were detected by in situ hybridization of the Y chromosome. We compared these tissues with biopsies of essentially normal skin and intestine, and two rare carcinomas with low rates of lymphatic endothelial proliferation that were derived from individuals with gender-mismatched bone marrow transplants. Here, we provide evidence for the participation of recipient-derived lymphatic progenitor cells in renal transplants. In contrast, lymphatic vessels of normal tissues and those around post-transplant carcinomas did not incorporate donor-derived progenitors. This indicates a stepwise mechanism of inflammation-associated de novo lymphangiogenesis, implying that potential lymphatic progenitor cells derive from the circulation, transmigrate through the connective tissue stroma, presumably in the form of macrophages, and finally incorporate into the growing lymphatic vessel.

Cardiorespiratory fitness, independently of total adiposity, body fat distribution and exercise intensity, determines liver fat content in humans, suggesting that fitness and liver fat are causally related to each other. Moreover, measurement of fitness at baseline predicts the effectiveness of a lifestyle intervention in reducing hepatic steatosis in patients with NAFLD.

Considering the "semimalignant" character of this entity and the poor treatment results in patients with recurrent tumors, marginal or wide resection for primary treatment is recommended. The superior imaging quality of MRI greatly facilitates preoperative planning.