Selective eosinophil recruitment is the result of orchestrated events involving cell adhesion molecules, chemokines, and their receptors. The mechanisms by which chemokines regulate eosinophil adhesion and migration via integrins are not fully understood. In our study, we examined the effect of CCR3-active chemokines on eosinophil adhesion to VCAM-1 and BSA under both static and flow conditions. When eotaxin-2 or other CCR3-active chemokines were added to adherent eosinophils, it induced rapid and sustained eosinophil detachment from VCAM-1 in a concentration-dependent manner. Adhesion was detectably reduced within 3 min and was further reduced at 10–60 min. Simultaneously, eotaxin-2 enhanced eosinophil adhesion to BSA. Preincubation of eosinophils with the CCR3-blocking mAb 7B11 completely prevented chemokine-induced changes in adhesion to VCAM-1 and BSA. Using a different protocol, pretreatment of eosinophils with chemokines for 0–30 min before their use in adhesion assays resulted in inhibition of VCAM-1 adhesion and enhancement of BSA adhesion. By flow cytometry, expression of α4 integrins and a β1 integrin activation epitope on eosinophils was decreased by eotaxin-2. In a flow-based adhesion assay, eotaxin-2 reduced eosinophil accumulation and the strength of attachment to VCAM-1. These results show that eotaxin-2 rapidly reduced α4 integrin function while increasing β2 integrin function. These findings suggest that chemokines facilitate migration of eosinophils by shifting usage away from β1 integrins toward β2 integrins.
The results indicate that tumor budding makes a greater contribution to progression in non-polypoid than in polypoid growth carcinomas, with possible involvement of lymph node metastasis.
BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, known to be associated with a markedly increased risk of colorectal carcinoma development. METHODS: Using proteomic analysis with two-dimensional gel electrophoresis and mass spectrometry, differentially expressed proteins were assessed between UC-associated cancer and sporadic colon cancer cell lines. Western blot and immunostaining were performed for confirming the expression. RESULTS: Heat-shock protein of 47 kDa (HSP47) was identified as one of the proteins expressed more highly in UC-associated cancer cell lines, and an immunohistochemical examination confirmed significantly higher levels of HSP47 in UC-associated colon cancers than in sporadic counterparts, the expression increasing with a progression of neoplastic lesions. Heat-shock protein of 47 kDa was further found to be coexpressed with type I collagen in the cytoplasm, and both HSP47 and type I collagen were released from cultured cells into the culture medium. CONCLUSION: These results suggest that overexpression of HSP47 is a unique characteristic of UC-associated carcinoma related to type I collagen synthesis, with possible clinical applications.
We measured changes in plasma ghrelin and GH concentrations in mature Holstein cows and 3-mo-old female Holstein calves fed at scheduled times. Our objective was to determine the characteristics of ghrelin secretion in dairy cattle and its influence on GH. Animals were fed at 0800 and 1600 for 2 wk before and during experiments. Plasma was sampled for 24 h at 2-h intervals in Exp. 1. In mature cows, plasma ghrelin concentrations decreased (P < 0.01) just after 0800 but not at the 1600 feeding. Ghrelin concentrations were lower (P < 0.01) in calves than in mature cows and they did not decrease after feeding in calves. The temporal relationship between ghrelin and GH remained unclear. In Exp. 2, plasma was sampled 2 h before and after both morning and evening feedings at 20-min intervals. Plasma ghrelin concentrations decreased (P < 0.05) 40 min after 0800 feeding and 60 min after 1600 feeding in mature cows. These results indicate that in mature cows, plasma ghrelin concentration decreased after feeding, but this decrease was not evident in 3-mo-old calves. Further studies are required to define the relationship between plasma ghrelin and GH concentrations.
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