ABSTRACT
Objective To discuss a method to induce vascular remodeling (intimal regeneration) after partial ligation of the left common carotid artery. Methods Forty 8-week-old male C57BL / 6 J mice were randomly divided into 6 groups: normal group (WT), sham group (sham), 4 weeks, 8 weeks, 10 weeks and 12 weeks postoperative groups. Only the internal carotid, external carotid and occipital arteries in the four distal branches of the left common carotid artery (LCA) were ligated, and the superior thyroid artery was retained, resultsing in intimal neovascularization and vascular remodeling of the left common carotid artery. The changes of body weight and forage were observed after operation. Morphological changes of blood vessels were observed by HE staining. The aggregation of collagen fibers in blood vessels was observed by sirius red staining. Results In addition to the WT group, the weight and dietary quantity of other groups were reduced 1-2 days after the operation, and began to rise from the third day, while the sham group began to rise from the second day. HE staining showed that no new intima was formed in the left common carotid artery of sham group and WT group, and thickening of intima and media layer and stenosis of the nasal cavity were observed in the 4, 8, 10 and 12 weeks groups after partial ligation. There was no intima thickening in the unligated carotid artery on the right side, but there was an enlargement of the lumen. This sirius red stain demonstrated collagen accumulation in the intima and tunica media. Conclution Partial ligation of the left common carotid artery can establish a mouse model of arterial endothelial injury with obvious intima regeneration.
ABSTRACT
<p><b>Background</b>Dendritic cells (DCs) play an important role in host defense against pathogen infection. DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (SIGN) is a group II C-type lectin receptor and specifically expressed on the surface of DCs. This study aimed to determine whether DC-SIGN affects intracellular signaling activation, Th1/Th2 imbalance and aspergillus immune evasion in aspergillus infection, and explore the application of DC-SIGN-modified DCs in immunotherapy.</p><p><b>Methods</b>DCs were first obtained from the mononuclear cells of peripheral blood. The interferon (IFN)-γ and dexamethasone (Dex) were used to stimulate DCs. The expression of DC-SIGN, Th1 and Th2 cytokines, and the capacity of DCs in stimulating T cells proliferation and phagocytosis, and nuclear factor (NF)-κB activation were analyzed. In addition, adenovirus expression vector Ad-DC-SIGN was generated to transfect DCs. Mannan was used to block DC-SIGN signaling for confirming the involvement of DC-SIGN function in Aspergillus fumigatus (Af)-induced DCs maturation. The unpaired, two-tailed Student's t-test was used in the comparisons between two groups.</p><p><b>Results</b>Exogenous IFN-γ could activate Af-induced DCs and promote the Th0 cells toward Th1 profile (interleukin [IL]-12 in IFN-γ/Af group: 50.96 ± 4.38 pg/ml; control/Af group: 29.70 ± 2.00 pg/ml, t = 10.815, P < 0.001). On the other hand, Dex inhibited the secretion of Th2 cytokines (IL-10 in Dex/Af group: 5.27 ± 0.85 pg/ml; control/Af group: 15.14 ± 1.40 pg/ml, t = 14.761, P < 0.001)), and successfully caused immunosuppression. After transfection with Ad-DC-SIGN, DCs have improved phagocytosis (phagocytosis rates in Ad-DC-SIGN group: 74.0% ± 3.4%; control group: 64.7% ± 6.8%, t = 3.104, P = 0.013). There was more Th1 cytokine secreted in the Af-induced DC-SIGN modified DCs (IL-12 in Ad-DC-SIGN/Af group: 471.98 ± 166.31 pg/ml; control/Af group: 33.35 ± 5.98 pg/ml, t = 6.456, P = 0.001), correlated to the enhanced NF-κB activation.</p><p><b>Conclusion</b>Overexpressing DC-SIGN in DCs had a protective function on aspergillosis.</p>