Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses

Alpha-1-acid glycoprotein (AGP-1) is a major positive acute phase glycoprotein with unknown functions that likely play a role in inflammation. We tested its involvement in a variety of inflammatory responses using human AGP-1 purified to apparent homogeneity and confirmed its identity by immunoblotting and mass spectrometry. AGP-1 alone upregulated MAPK signaling in murine peritoneal macrophages. However, when given in combination with TLR ligands, AGP-1 selectively augmented MAPK activation induced by ligands of TLR-2 (Braun lipoprotein) but not TLR-4 (lipopolysaccharide). In vivo treatment of AGP-1 in a murine model of sepsis with or without TLR-2 or TLR-4 ligands, selectively potentiated TLR-2-mediated mortality, but was without significant effect on TLR-4-mediated mortality. Furthermore, in vitro, AGP-1 selectively potentiated TLR-2 mediated adhesion of human primary immune cell, neutrophils. Hence, our studies highlight a new role for the acute phase protein AGP-1 in sepsis via its interaction with TLR-2 signaling mechanisms to selectively promote responsiveness to one of the two major gram-negative endotoxins, contributing to the complicated pathobiology of sepsis.     

Multi-cellularity in cardiac tissue engineering,how close are we to native heart tissue?

Journal of Muscle Research and Cell Motility - Tissue engineering is a complex field where the elements of biology and engineering are combined in an attempt to recapitulate the native environment...     

Costameres,dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing

Journal of Muscle Research and Cell Motility - The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. For...     

Tryptophan-kynurenine profile in pediatric autoimmune hepatitis

Immunologic Research - The impairment of regulatory T cells (Tregs) is a characteristic feature of autoimmune hepatitis (AIH), and the degradation of tryptophan (Trp) to kynurenine (Kyn), by gamma...     

数字病理扫描在颈动脉粥样硬化斑块组织学研究中的应用

目的颈动脉粥样硬化斑块的形成是脑血管病变的独立危险因素之一。对颈动脉内膜剥脱术(carotid endarterectomy,CEA)斑块进行充分的组织学判读和研究,将有助于全面把握CEA斑块的组织学表现,进而推进临床辅助诊断。方法本文我们将运用数字病理扫描仪对CEA斑块的切片经H&E染色后进行扫描,介绍数字病理扫描在CEA斑块组织学研究中的应用。结果经数字病理扫描所得的图片,有助于全面掌握和保存CEA斑块组织切片的全层面信息;在软件的帮助下有助于非常方便地测量斑块内各成分的大小;有助于精确评估斑块的狭窄程度。结论综上,数字病理成像应用于CEA斑块,结合MRI,有助于高效且准确地判读斑块组成和预测斑块稳定性,亦有助于人工智能的训练。