1型糖尿病的细胞和分子致病机理

1型糖尿病是把自身免疫系统对胰岛β细胞进行特异性损伤作为特征的自身免疫疾病,其中β细胞自身抗原,T淋巴细胞,B淋巴细胞及巨噬细胞对胰岛β细胞的损伤起重要作用。     

In vitro study of immunosuppressive effect of apoptotic cells

INTRODUCTION Apoptosis plays an important role in differen- tiation, development and pathophysiological proc- esses such as inflammation, neoplasia and autoim- mune diseases. For a long time, apoptotic cells per se and the clearance of apoptotic cells had been viewed as neutral in immune response. Recently many in- vestigations suggested that apoptotic cells actively regulate the immune response (Voll et al., 1997; Fadok et al., 1998; 2000; Byrne and Reen, 2002). Apoptotic cells release …     

Expression and preliminary functional analysis of Siglec-F on mouse macrophages

Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a mouse functional paralog of human Siglec-8 that induces apoptosis in human eosinophils, and therefore may be useful as the basis of treatments for a variety of disorders associated with eosinophil hyperactivity, such as asthma. The expression pattern and functions of this protein in various cell types remain to be elucidated. The aim of this study was to determine the expression of Siglec-F on mouse macrophages by immunocytochemical staining, and also to investigate the effects of Siglec-F engagement by a Siglec-F antibody on phagocytic activity of macrophages. The results showed that Siglec-F expression was detected on mouse alveolar macrophages, but not on peritoneal macrophages. Furthermore, Siglec-F engagement did not affect the phagocytic activity of alveolar macrophages in the resting state or in the activated state following stimulation by the proinflammatory mediator tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS). Siglec-F expression on alveolar macrophages may be a result of adaptation. Macrophages actively regulate immune responses via production of cytokines. Therefore, further investigation of the effects of Siglec-F engagement on immune mediators or cytokines released by alveolar macrophages is required.     

In vitro study of immunosuppressive effect of apoptotic cells

Recent studies revealed that apoptotic cells are actively involved in immunosuppression and anti-inflammation. After being phagocytosed by macrophages, apoptotic cells can actively regulate cytokines secretion from lipopolysaccharide (LPS)-stimulated macrophages in which the secretion of immunosuppressive cytokines such as interleukin-10 (IL-10) is increased while the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα), interleukin-1beta (IL-1β) and leukin-8 (IL-8) are suppressed. In this paper, we first present evidence that phagocytosed apoptotic cells regulate cytokine secretion of LPS-stimulated macrophages, but also inhibit the activation of T lymphocytes stimulated by ConA. These data suggest that apoptotic cells can alter the biological behavior of macrophages which gain immunosuppressive property. Project supported by the National Basic Research Program (973) of China (No. 2003CB515500) and the National Natural Science Foundation of China (No. 30371358)     

An in vitro model mimicking the complement system to favor directed phagocytosis of unwanted cells

BackgroundOpsonization, is the molecular mechanism by which target molecules promote interactions with phagocyte cell surface receptors to remove unwanted cells by induced phagocytosis. We designed an in vitro system to demonstrate that this procedure could be driven to eliminate adipocytes, using peptides mimicking regions of the complement protein C3b to promote opsonization and enhance phagocytosis. Two cell lines were used: (1) THP-1 monocytes differentiated to macrophages, expressing the C3b opsonin receptor CR1 in charge of the removal of unwanted coated complexes; (2) 3T3-L1 fibroblasts differentiated to adipocytes, expressing AQP7, to evaluate the potential of peptides to stimulate opsonization. (3) A co-culture of the two cell lines to demonstrate that phagocytosis could be driven to cell withdrawal with high efficiency and specificity.ResultsAn array of peptides were designed and chemically synthesized p3691 and p3931 joined bound to the CR1 receptor activating phagocytosis (p < 0.033) while p3727 joined the AQP7 protein (p < 0.001) suggesting that opsonization of adipocytes could occur. In the co-culture system p3980 and p3981 increased lipid uptake to 91.2% and 89.0%, respectively, as an indicator of potential adipocyte phagocytosis.ConclusionsThis in vitro model could help understand the receptor–ligand interaction in the withdrawal of unwanted macromolecules in vivo. The adipocyte-phagocytosis discussed may help to control obesity, since peptides of C3b stimulated the CR1 receptor, promoting opsonisation and phagocytosis of lipid-containing structures, and recognition of AQP7 in the differentiated adipocytes, favored the phagocytic activity of macrophages, robustly supported by the co-culture strategy.How to cite: Bartsch IM, Perelmuter K, Bollati-Fogolin M, et al. An in vitro model mimicking the complement system to favor directed phagocytosis of unwanted cells. Electron J Biotechnol 2021;49. https://doi.org/10.1016/j.ejbt.2020.09.010.