Autoantibodies to red blood cell surface Glycophorin A impact the activation poise of circulating leukocytes

Transfusion ◽  
2021 ◽  
Author(s):  
Matthew N. Klein ◽  
Emily J. Larkin ◽  
Juliana N. Marshall ◽  
Xiaoxuan Fan ◽  
Philippe Parry ◽  
...  
Keyword(s):  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Glycophorin A

scholarly journals Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Maria del Pilar Quintana ◽  
Jun-Hong Ch’ng ◽  
Kirsten Moll ◽  
Arash Zandian ◽  
Peter Nilsson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell

scholarly journals EFFECT OF ARABICA AND CANEPHORA COFFEE BEAN EXTRACTS TOWARDS MODIFICATION OF RED BLOOD CELL SURFACE ANTIGENS

2018 ◽  
Vol 9 (5) ◽  
pp. 91-95 ◽  
Author(s):  
Praveen Kumar Vemuri ◽  
Sanjay Madala ◽  
Vijaya Lakshmi Bodiga ◽  
Suryanarayana Veeravalli ◽  
Nithin Chand Kurra
Keyword(s):  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Surface Antigens ◽  
Coffee Bean ◽  
Cell Surface Antigens

scholarly journals The Cytoplasmic Region of Plasmodium falciparum SURFIN4.2 Is Required for Transport from Maurer’s Clefts to the Red Blood Cell Surface

2015 ◽  
Vol 43 (4) ◽  
pp. 265-272 ◽  
Author(s):  
Wataru Kagaya ◽  
Shinya Miyazaki ◽  
Kazuhide Yahata ◽  
Nobuo Ohta ◽  
Osamu Kaneko
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Cytoplasmic Region ◽  
Maurer's Clefts

scholarly journals Plasmodium falciparum erythrocyte-binding antigen 175 triggers a biophysical change in the red blood cell that facilitates invasion

2017 ◽  
Vol 114 (16) ◽  
pp. 4225-4230 ◽  
Author(s):  
Marion Koch ◽  
Katherine E. Wright ◽  
Oliver Otto ◽  
Maik Herbig ◽  
Nichole D. Salinas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Blood Cell ◽  
Signaling Pathways ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Red Cell ◽  
Biophysical Properties ◽  
Parasite Invasion ◽  
Bending Modulus ◽  
Erythrocyte Binding

Invasion of the red blood cell (RBC) by the Plasmodium parasite defines the start of malaria disease pathogenesis. To date, experimental investigations into invasion have focused predominantly on the role of parasite adhesins or signaling pathways and the identity of binding receptors on the red cell surface. A potential role for signaling pathways within the erythrocyte, which might alter red cell biophysical properties to facilitate invasion, has largely been ignored. The parasite erythrocyte-binding antigen 175 (EBA175), a protein required for entry in most parasite strains, plays a key role by binding to glycophorin A (GPA) on the red cell surface, although the function of this binding interaction is unknown. Here, using real-time deformability cytometry and flicker spectroscopy to define biophysical properties of the erythrocyte, we show that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of the red cell and a reduction in the bending modulus of the cell’s membrane. We isolate the changes in the cytoskeleton and membrane and show that reduction in the bending modulus is directly correlated with parasite invasion efficiency. These data strongly imply that the malaria parasite primes the erythrocyte surface through its binding antigens, altering the biophysical nature of the target cell and thus reducing a critical energy barrier to invasion. This finding would constitute a major change in our concept of malaria parasite invasion, suggesting it is, in fact, a balance between parasite and host cell physical forces working together to facilitate entry.

Simultaneous Camouflage of Major and Minor Antigens on Red Blood Cell Surface With Activated mPEGs

2014 ◽  
Vol 12 (2) ◽  
Author(s):  
Zahra Gholami ◽  
Sameereh Hashemi Najafabadi ◽  
Masoud Soleimani
Keyword(s):  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell

The use of the anti-Glycophorin a antibody in the detection of red blood cell residues in human soft tissue lesions decomposed in air and water: a pilot study

2011 ◽  
Vol 51 (1_suppl) ◽  
pp. 16-19 ◽  
Author(s):  
A Taborelli ◽  
S Andreola ◽  
A Di Giancamillo ◽  
G Gentile ◽  
C Domeneghini ◽  
...  
Keyword(s):  
Pilot Study ◽  
Soft Tissue ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Glycophorin A ◽  
Soft Tissue Lesions ◽  
Human Soft Tissue

δ-Toxin, unlike melittin, has only hemolytic activity and no antimicrobial activity: Rationalization of this specific biological activity

1993 ◽  
Vol 13 (4) ◽  
pp. 245-250 ◽  
Author(s):  
Vishnu Mukund Dhople ◽  
Ramakrishnan Nagaraj
Keyword(s):  
Antimicrobial Activity ◽  
Biological Activity ◽  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Synthetic Peptide ◽  
Lipid Membrane ◽  
Cell Surfaces ◽  
Gram Negative ◽  
Micro Organisms

The antimicrobial activity of a synthetic peptide corresponding to δ-hemolysin had been examined. The peptide did not exhibit antimicrobial activity against gram negative and gram positive micro-organisms unlike other hemolytic peptides like melittin. This lack of antibacterial activity arises due to the inability of δ-hemolysin to perturb the negatively charged bacterial cell surface and permeabilize the bacterial plasma membrane. However, the red blood cell surface has a structure considerably different from bacteria, and does not act as a barrier to molecules reaching the lipid membrane. Hence δ-toxin can lyse erythrocytes. Thus, the specificity in biological activity has been rationalized in terms of differences, in the interaction of the toxin with the bacterial and red blood cell surfaces.

scholarly journals Assessment of the Effect of Crizanlizumab on Red Blood Cell Adhesion to Endothelial Cells Using a Standardized Endothelium-on-a-Chip Microfluidic Platform

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2021-2021
Author(s):  
Erdem Kucukal ◽  
Aaron Wolfe ◽  
Ryan Kocevar ◽  
Lalitha V Nayak ◽  
Andreas Bruederle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Stock Options ◽  
Microfluidic Channels ◽  
Blood Samples ◽  
Privately Held

Abstract Background: Chronic upregulation of P-selectin (P-sel) on blood cells and the endothelium leads to abnormal red blood cell (RBC) adhesion to endothelial cells, significantly contributing to vaso-occlusive crises (VOCs), which are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). Crizanlizumab (criz, a.k.a. SEG101) is a humanized anti-P-sel monoclonal antibody and has recently been approved by the Food and Drug Administration to reduce the frequency of VOCs in SCD patients. Here, we report in vitro assessment of the effect of criz on patient-specific RBC adhesion to heme-activated human endothelial cells using a standardized endothelialized microfluidic platform, the Endothelium-on-a-chip. Methods: Whole blood samples were collected from 13 subjects with SCD (13 HbSS and 1 HbSC) in EDTA vacutainers. RBCs were isolated via centrifugation from whole blood and then resuspended in basal cell culture medium (EBM, Lonza, Morristown, USA) at a hematocrit of 20% buffered with 10 mM of HEPES. Human umbilical vein endothelial cells (HUVECs) were obtained from Lonza and cultured within the microfluidic channels at 15 dyne/cm 2 for at least 48 hours prior to experiments. For long-term activation, HUVECs were treated with 40 µM heme for 4 hours +/- 100 µg/ml criz for 1 hour followed by injection of blood samples through the microfluidic channels. For short-term activation, blood samples were supplemented with 40 µM heme +/- 100 µg/ml criz and injected through the microfluidic channels for 15 minutes. Thereafter, non-adherent RBCs were rinsed via either only heme-containing EGM or heme- and criz-containing EGM, and the remaining RBCs were quantified based on published methods [1]. Student's t-test was used to calculate statistical significance. Results: We found that 4-hour heme activation of HUVECs resulted in significantly elevated RBC adhesion compared to baseline although adhesion levels were heterogenous among the patient population (Fig. 1A, 1671±522 vs 17±4, p<0.05). Treatment of 4-hour heme-activated HUVECs with criz did not significantly decrease RBC adhesion (Fig. 1A, 1170±413 vs 1671±522, p>0.05), while we observed lower RBC adhesion to criz treated HUVECs for certain subjects (Fig. 1B). By contrast, criz treatment significantly reduced the number of adherent RBCs to 15-min heme-activated HUVECs (Fig. 1C, 135±40 vs 1513±617, p<0.05). Next, we assessed whether criz would disrupt already established adhesive interactions between RBCs and 15-min heme-activated HUVECs. To do so, we first allowed RBCs to adhere to heme-activated HUVECs (for 15-min) and then rinsed the microchannels (at 10 μl/min) via either a heme- or both heme- and criz-containing solution (for 15 min). We then quantified the number of adherent RBCs at min=0 and min=15. While only 10% of the adherent RBCs remained in the microchannels following a 15-minute wash with criz, this ratio was 60% without criz (Fig. 1E). Discussion: Our results show that the magnitude of inhibition of RBC adhesion to HUVECs with criz correlated with the duration of heme-activation (4 hours vs 15 minutes). This is likely due to variable levels of different adhesion molecules on acute or chronically activated HUVECs. For instance, it has been shown that P-selectin is rapidly translocated to the cell surface following heme activation [1], but its concentration on cell surface significantly decays with time. Previous experiments have shown that sickle RBCs can adhere to cell adhesion molecules such as ICAM-1 [2], which mechanistically may play a role in the case of a chronically activated endothelium. We are currently exploring whether criz would also reduce RBC adhesion to acutely activated endothelial cells that are under chronic stress. These preliminary results suggest that the Endothelium-on-a-chip, as partner in novel therapeutic studies, could help monitoring dynamics of targeted therapies in SCD patients during drug development and in clinical trials. Acknowledgements: This work was funded by Novartis. The authors would like to thank the Ohio Third Frontier Technology Validation and Start-up Fund (TVSF) and National Science Foundation Phase-I Small Business Technology Transfer (STTR) award, which supported this work in part. Crizanlizumab was donated by Novartis. References: 1. Kucukal, E., et al., American Journal of Hematology, 2018. 93(8): p.1050-60 2. Kucukal, E., et al., Blood Advances, 2020. 4(15):3688-98 Figure 1 Figure 1. Disclosures Kucukal: BioChip Labs: Current Employment, Patents & Royalties. Kocevar: BioChip Labs: Current Employment. Nayak: BioChip Labs: Current Employment. Bruederle: Novartis Pharma AG: Current Employment. Zak: XaTek: Current Employment, Current holder of stock options in a privately-held company; BioChip Labs: Current Employment, Current holder of stock options in a privately-held company; TecTraum Inc: Current Employment, Current holder of stock options in a privately-held company. Gurkan: Dx Now Inc.: Patents & Royalties; Hemex Health, Inc.: Current Employment, Patents & Royalties; Biochip Labs: Patents & Royalties; Xatek Inc.: Patents & Royalties.

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