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Antitumor Effector Cells: Extravasation and Control of Metastasis
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
Theresa L. Whiteside, Ronald H. Goldfarb
Lymphocytes express a variety of surface receptors, some of which have been identified as signal transducing structures important for cell-cell or cell-substratum interactions. These adhesion receptors belong to several distinct families of membrane glycoproteins, and their structure and expression on lymphoid as well as nonlymphoid cells have been a subject of several recent and comprehensive reviews (3,4). One family of cell surface glycoproteins that mediate cell adhesion of lymphocytes are integrins, heterodimeric molecules similar in structure to immunoglobulins and consisting of noncovalently associated a and ß subunits. Various combinations of a and ß subunits derived from at least 16 integrins are responsible for great diversity of integrins among cell types (5). The integrins expressed on lymphocytes belong to the ß1, family, also referred to as the very late antigen (VLA) family, and the ß2 family, which includes lymphocyte function-associated antigen-1 (LFA-1), Mac-1, and p150/95 (6,7).
Pregnancy-Related Proteins Detected by Their Biological Activities
Published in Gábor N. Than, Hans Bohn, Dénes G. Szabó, Advances in Pregnancy-Related Protein Research, 2020
Vitamin B12 is important for the functioning of certain basic metabolic processes leading to normal growth and development. In the blood stream, vitamin B12 combines with a serum protein transcobalamin II and is thus transported to peripheral tissues. Many cells have specific receptors for transcobalamin II, enabling them to internalize the complex. In human placental membrane preparations, a saturable high affinity binding site for transcobalamin II-vitamin B12 complexes was first described by Friedman et al.225 The receptor was shown to be strongly dependent on divalent cations since EDTA abolished binding. The receptor was also sensitive to trypsin, and to a lesser extent neuraminidase treatment, but insensitive to phospholipase C; binding activity was retained, however, following solubilization of placental membranes in Triton X-100. These characteristics are in accord with the receptor being a peripheral membrane glycoprotein. Characterization of the receptor for transcobalamin II isolated from human placenta was reported in 1978 by Seligman and Allen.226
The Type II Pneumocyte
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
In all species described so far, while type I cells are characterized by a smooth surface, the apex of type II cells bears numerous short microvilli (0.27 μm ± 0.01 in the fetal cultured rat lung) (Figure 2). A core of actin-like filaments that are in continuity with the dense network lying near the cell surface has been demonstrated in these microvilli.40 Type II cell apical membrane also differs from that of type I cells at the molecular level. Indeed, the use of various exogenous agglutinins, from vegetal or animal origin, showed that the two alveolar cell types exhibit different lectin-binding patterns,41–44 as summarized in Table 1. In addition to providing accurate markers for type II cell tracing in the course of fetal lung development, alveolar epithelium repair, or in culture conditions, this specificity demonstrates the presence of different mucopolysaccharide species at their surface. Such lectin-binding glycoproteins — more specifically, proteins binding to Maclura pomifera agglutinin (MPA) — have recently been isolated and characterized in the rat45 and rabbit.46 These molecules, with a molecular mass of about 200 kDa, are integral membrane glycoproteins. Their function is presently unknown; one possibility is that they might act as ion channels.46
The utility of platelet activation biomarkers in thrombotic microangiopathies
Published in Platelets, 2022
Mohammad Al-Tamimi, Jianlin Qiao, Elizabeth E. Gardiner
This platelet surface membrane glycoprotein binds the A1 domain of VWF and a host of other vascular proteins (αMβ2, several coagulation factors, and P-selectin) and is downregulated by metalloproteinase‐mediated cleavage and release of a soluble fragment named glycocalicin [25,59]. Measuring plasma glycocalicin levels by ELISA has been reported; however, interpretation of these values remains challenging due to the significant variation in levels of glycocalicin in healthy controls as well as in patient cohorts [60]. Platelet GPIbα levels were shown to be similar between samples from TTP patients and controls, but were significantly reduced in platelets from two patients with acute TTP [52,61]. Caplacizumab, which inhibits the VWF-GPIbα interaction, has been approved for treatment of acute acquired TTP [29,30,62]. As VWF engagement of GPIb-IX-V, particularly under shear stress is likely to activate shedding pathways [63], it will be of great interest to evaluate changes in plasma glycocalicin levels in patients before and after receipt of caplacizumab. The elevated plasma level of GPIbα in TMA patients has not been documented but are expected to be high similar to other release markers.
Proteomics-inspired precision medicine for treating and understanding multiple myeloma
Published in Expert Review of Precision Medicine and Drug Development, 2020
Matthew Ho, Giada Bianchi, Kenneth C. Anderson
Glycosylation is an important PTM. Altered serum and membrane glycoprotein profiles of malignant cells have been implicated in cancer progression and metastasis [100]. The application of glycoproteomics in the discovery of MM biomarkers, both at the immunoglobulin and cell membrane level, has garnered significant interest in recent years [11]. M-protein, a pathognomonic feature of MM, undergoes heavy glycosylation at both the Fc (fragment crystallizable) and Fab (fragment antigen-binding) regions [11]. Biantennary N-glycosylation at asparagine 297 in the Fc region provides structural stability, affects Fc gamma receptor binding on effector cells, and therefore regulates the function of immunoglobulins [101]. In contrast, absent immunoglobulin core fucosylation increased binding to Fc gamma receptor IIIa (by up to 50-fold), resulting in enhanced antibody-dependent cellular cytotoxicity activity [102]. Glycosylation at the Fab region regulates antigen binding, immune complex formation, and increases immunoglobulin half-life [103]. These findings highlight the importance of studying immunoglobulin glycosylation particularly with the increasing use of immunotherapy in MM.
Small-molecule PD-L1 inhibitor BMS1166 abrogates the function of PD-L1 by blocking its ER export
Published in OncoImmunology, 2020
Fang-Fang Chen, Zheng Li, Dawei Ma, Qiang Yu
PD-L1 is a type I integral membrane glycoprotein which is extensively N-glycosylated at four conserved Asparagine residues.23,27 To investigate whether the alteration of PD-L1 pattern resulted from N-glycosylation inhibition by BMS1166, we treated the PC9/PD-L1 cells with tunicamycin (TM), a pan-N-linked glycosylation inhibitor, or the peptide-N-glycosidase (PNGase F), which removes the entire N-glycan structure from peptides.28,29 We found that all the PD-L1 protein bands on the Western blot, including the BMS1166-generated 43-kDa bands, were totally shifted to an approximately 34-kDa protein bands by either TM or the PNGase F treatment (Figure 3(a)), close to its unmodified form,27 suggesting that BMS1166 partially inhibited PD-L1 N-glycosylation.