scholarly journals Blood donor variability is a modulatory factor for P. falciparum invasion phenotyping assays

2020 ◽  
Author(s):  
Laty G. Thiam ◽  
Prince B. Nyarko ◽  
Kwadwo A. Kusi ◽  
Makhtar Niang ◽  
Yaw Aniweh ◽  
...  

AbstractHuman erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different backgrounds. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which presents a challenge for conducting large-scale comparative studies. Here, we used erythrocytes of different blood groups harboring different hemoglobin genotypes to assess the relative contribution of blood donor variability in P. falciparum invasion phenotyping assays. For each donor, we investigated the relationship between parasite invasion phenotypes and erythrocyte phenotypic characteristics, including; the expression levels of surface receptors (e.g. the human glycophorins A and C, the complement receptor 1 and decay accelerating factor), blood groups (e.g. ABO/Rh system), and hemoglobin genotypes (e.g. AA, AS and AC). Across all donors, there were significant differences in invasion efficiency following treatment with either neuraminidase, trypsin or chymotrypsin relative to the control erythrocytes. Primarily, we showed that the levels of key erythrocyte surface receptors and their sensitivity to enzyme treatment, significantly differed across donors. However, invasion efficiency correlated neither with susceptibility to enzyme treatment nor with the levels of the selected erythrocyte surface receptors. Upon further analysis, we found no relationship between P. falciparum invasion phenotype and blood group or hemoglobin genotype.ImportanceAssays to decipher P. falciparum invasion phenotypes are of great importance in the quest for an efficient malaria vaccine. Malaria associated mortality is mainly attributed to the blood stage of the parasite’s life cycle, a major focus of vaccine development strategies. Further, testing and validating blood stage vaccines necessitates conducting large-scale studies in endemic countries. However, comparing results from such studies is challenged by the lack of standard assays. As human erythrocytes play a pivotal role in P. falciparum invasion assays, the need to investigate the effect of blood donor variability in the outcome of such assays is apparent. The significance of our study is in reporting the absence of relationship between P. falciparum invasion efficiency and commonly shared erythrocyte features across different erythrocyte donors, therefore emphasizing the need to consider erythrocyte donor uniformity and to anticipate challenges associated to blood donor variability in early stages of large-scale study design.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laty G. Thiam ◽  
Prince B. Nyarko ◽  
Kwadwo A. Kusi ◽  
Makhtar Niang ◽  
Yaw Aniweh ◽  
...  

AbstractHuman erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different individuals. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which represents a challenge for conducting large-scale comparative studies. Here, we used erythrocytes of different blood groups harboring different hemoglobin genotypes to assess the relative contribution of blood donor variability in P. falciparum invasion phenotyping assays. For each donor, we investigated the relationship between parasite invasion phenotypes and erythrocyte phenotypic characteristics, including the expression levels of surface receptors (e.g. the human glycophorins A and C, the complement receptor 1 and decay accelerating factor), blood groups (e.g. ABO/Rh system), and hemoglobin genotypes (e.g. AA, AS and AC). Across all donors, there were significant differences in invasion efficiency following treatment with either neuraminidase, trypsin or chymotrypsin relative to the control erythrocytes. Primarily, we showed that the levels of key erythrocyte surface receptors and their sensitivity to enzyme treatment significantly differed across donors. However, invasion efficiency did not correlate with susceptibility to enzyme treatment or with the levels of the selected erythrocyte surface receptors. Furthermore, we found no relationship between P. falciparum invasion phenotype and blood group or hemoglobin genotype. Altogether, our findings demonstrate the need to consider erythrocyte donor uniformity and anticipate challenges associated with blood donor variability in early stages of large-scale study design.


1977 ◽  
Vol 146 (1) ◽  
pp. 277-281 ◽  
Author(s):  
L H Miller ◽  
J D Haynes ◽  
F M McAuliffe ◽  
T Shiroishi ◽  
J R Durocher ◽  
...  

Human erythrocytes lacking various blood group determinants were susceptible to invasion by Plasmodium falciparum including Duffy-negative erythrocytes that are refractory to invasion by Plasmodium knowlesi. Erythrocytes treated with trypsin or neuraminidase had reduced susceptibility of P. falciparum and normal susceptibility to P. knowlesi. Chymotrypsin treatment (0.1 mg/ml) blocked invasion only by P. knowlesi. The differential effect of enzymatic cleavage of determinats from the erythrocyte surface on invasion by these parasites suggests that P. falciparum and P. knowlesi interact with different determinants on the erythrocyte surface.


1968 ◽  
Vol 10 (6) ◽  
pp. 829-843 ◽  
Author(s):  
R. A. Fisher ◽  
H. Harris ◽  
M. Houldsworth ◽  
M. D. Lilly ◽  
P. Dunnill

2012 ◽  
Vol 1 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Rayhana Sultana ◽  
Zaida Rahman ◽  
Dipok Kumar Sannyal ◽  
Mohammad Abdullah Al Masud ◽  
Golam Morshed Molla ◽  
...  

Background: The distribution pattern of ABO and Rh-D blood group in our country including the tribal people is not fully established as elaborated and large scale studies have not been carried out on it. Therefore this study was designed to observe the distribution pattern of ABO and Rh-D blood groups among the Garo tribes of Mymensingh and general people of Dhaka city. Objectives: To determine and to compare the distribution pattern of ABO and Rh-D blood groups among the Garo tribal people of Mymensingh and general people of Dhaka city and to compare this distribution between this two groups. Materials and Methods: This observational study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2008 to June 2009. After proper ethical consideration total 900 Garo people of Mymensingh and 784 general people of Dhaka city were included in this study. The Garo localities and the general people of Dhaka city were selected by systematic random sampling. ABO and Rh-D blood groups were determined by the antigen antibody agglutination test of slide method. Chi square statistical analyses were done to compare the results of ABO blood group systems between the Garo people and general people of Dhaka city. Results: This study revealed that there are significant variations in the distribution of ABO and Rh-D blood groups between the Garo tribal people of Mymensingh and the general people of Dhaka city. In this study it was observed that blood group ‘A’ was apparently predominant in Garo population, while blood group ‘B’ was predominant in general population (p<0.001), blood group ‘AB’ and ‘O’ were almost similar in both groups. Rh typing of the participants reveals that majorities of both groups were Rh positive. Rh negative persons are rare in both populations, but it is extremely rare in the Garo population (0.9%). Conclusion: From the findings of the present study it can be concluded that distribution of ABO and Rh-D blood groups varies between the Garo tribal people and the general people of Dhaka city. DOI: http://dx.doi.org/10.3329/jemc.v1i1.11137J Enam Med Col 2011; 1(1): 31-35


2016 ◽  
Vol 17 (1) ◽  
pp. 105-109 ◽  
Author(s):  
J. Torabizade maatoghi ◽  
M. Paridar ◽  
M. Mahmodian Shoushtari ◽  
B. Kiani ◽  
B. Nori ◽  
...  

2016 ◽  
Vol 38 (4) ◽  
pp. 1425-1434 ◽  
Author(s):  
Elena Signoretto ◽  
Michela Castagna ◽  
Abdulla Al Mamun Bhuyan ◽  
Florian Lang

Background/Aims: The antihistaminic drug Terfenadine may trigger apoptosis of tumor cells, an effect unrelated to its effect on histamine receptors. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling triggering eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, and ceramide. The present study explored, whether Terfenadine is capable to trigger eryptosis. Methods: Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence, and ceramide abundance at the human erythrocyte surface utilizing specific antibodies. Hemolysis was quantified from haemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to Terfenadine (≥ 5 µM) significantly increased the percentage of annexin-V-binding cells and triggered hemolysis without significantly modifying the average forward scatter. Terfenadine (7.5 µM) significantly increased Fluo3-fluorescence, but did not significantly modify DCF fluorescence or ceramide abundance. The effect of Terfenadine on annexin-V-binding was significantly blunted but not abolished by removal of extracellular Ca2+. Exposure of human erythrocytes to Ca2+ ionophore ionomycin (1 µM, 15 min) triggered annexin-V-binding, an effect augmented by Terfenadine pretreatment (10 µM, 48 hours). Conclusions: Terfenadine triggers phospholipid scrambling of the human erythrocyte cell membrane, an effect in part due to entry of extracellular Ca2+ and in part due to sensitizing human erythrocyte cell membrane scrambling to Ca2+.


2001 ◽  
Vol 85 (06) ◽  
pp. 958-965 ◽  
Author(s):  
Dougald Monroe ◽  
Maureane Hoffman

SummaryBased on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that the protein coagulation factors direct and control the process with cells serving primarily to provide a phosphatidylserine containing surface on which the procoagulant complexes are assembled. By contrast, we propose a model in which coagulation is regulated by properties of cell surfaces. This model emphasizes the importance of specific cellular receptors for the coagulation proteins. Thus, cells with similar phosphatidylserine content can play very different roles in hemostasis depending on their complement of surface receptors. We propose that coagulation occurs not as a “cascade”, but in three overlapping stages: 1) initiation, which occurs on a tissue factor bearing cell; 2) amplification, in which platelets and cofactors are activated to set the stage for large scale thrombin generation; and 3) propagation, in which large amounts of thrombin are generated on the platelet surface. This cell based model explains some aspects of hemostasis that a protein-centric model does not.


2002 ◽  
Vol 4 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Walter Schubert

Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T-cell invasionin situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T-cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T-cells. This indicates, that the T-cell invasion is enciphered combinatorially in the T-cells' adhesive cell surface proteome fraction. Given 217possible combinations, the T-cell appears to have at its disposal a highly non-random restricted repertoire to specify migratory pathways at the cell surface. These higher-level order functions in the cellular proteome cannot be detected by large-scale protein profiling techniques from tissue homogenates. High-throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.


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