Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Abnormal Adherence of Sickle Erythrocytes to Cultured Vascular Endothelium: POSSIBLE MECHANISM FOR MICROVASCULAR OCCLUSION IN SICKLE CELL DISEASE
Robert P. Hebbel, … , James G. White, John W. Eaton
Robert P. Hebbel, … , James G. White, John W. Eaton
Published January 1, 1980
Citation Information: J Clin Invest. 1980;65(1):154-160. https://doi.org/10.1172/JCI109646.
View: Text | PDF
Article has an altmetric score of 6

Abnormal Adherence of Sickle Erythrocytes to Cultured Vascular Endothelium: POSSIBLE MECHANISM FOR MICROVASCULAR OCCLUSION IN SICKLE CELL DISEASE

  • Text
  • PDF
Abstract

The abnormal shape and poor deformability of the sickled erythrocyte (RBC) have generally been held responsible for the microvascular occlusions of sickle cell disease. However, there is no correlation between the clinical severity of this disease and the presence of sickled RBC. In searching for additional factors that might contribute to the pathophysiology of sickle cell disease, we have investigated the possibility that sickle RBC might be less than normally repulsive of the vascular endothelium. After RBC suspensions are allowed to settle onto plates of cultured human endothelial cells, normal RBC are completely removed by as few as six washes. In contrast, sickle RBC remain adherent despite multiple washes. On subconfluent culture plates, normal RBC are distributed randomly, whereas sickle RBC cluster around endothelial cells. Sickle RBC adherence is not enhanced by deoxygenation but does increase with increasing RBC density. The enzymatic removal of membrane sialic acid greatly diminishes the adherence of sickle RBC to endothelial cells, suggesting that sialic acid participates in this abnormal cell-cell interaction. Although net negative charge appears normal, sickle RBC mainfest an abnormal clumping of negative surface charge as demonstrated by localization of cationized ferritin. These abnormalities are reproduced in normal RBC loaded with nonechinocytogenic amounts of calcium. We conclude that sickle RBC adhere to vascular endothelial cells in vitro, perhaps caused by a calcium-induced aberration of membrane topography. This adherence may be a pathogenetic factor in the microvascular occlusions characteristic of sickle cell disease.

Authors

Robert P. Hebbel, Osamu Yamada, Charles F. Moldow, Harry S. Jacob, James G. White, John W. Eaton

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 1980 1978 1952 1949 Total
Citations: 1 2 4 5 3 7 7 10 7 15 7 10 2 5 4 10 8 9 5 5 3 5 7 7 7 8 6 6 7 6 2 6 7 4 7 7 2 13 10 16 7 6 4 6 1 1 1 1 289
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (15)

Title and authors Publication Year
Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease
Y Alapan, C Kim, A Adhikari, KE Gray, E Gurkan-Cavusoglu, JA Little, UA Gurkan
Translational Research 2016
VLA-4 blockade by natalizumab inhibits sickle reticulocyte and leucocyte adhesion during simulated blood flow
J White, S Krishnamoorthy, D Gupta, M Lancelot, N Moore, S Sarnaik, WE Hobbs, DR Light, P Hines
British Journal of Haematology 2016
Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion
MJ Telen, M Batchvarova, S Shan, PH Bovee-Geurts, R Zennadi, A Leitgeb, R Brock, M Lindgren
British Journal of Haematology 2016
INCREASED VASOOCCLUSIVE CRISIS IN “O” BLOOD GROUP SICKLE CELL DISEASE PATIENTS: ASSOCIATION WITH UNDERLYING THROMBOSPONDIN LEVELS
MA Huneini, A Pathare
Mediterranean journal of hematology and infectious diseases 2016
Crises in Sickle Cell Disease
EM Novelli, MT Gladwin
Chest 2016
Interactions of sickle red blood cells with neutrophils are stabilized on endothelial cell layers
VM Dominical, DM Vital, VT Garrido, AA Silveira, ST Olalla-Saad, FF Costa, N Conran
Blood Cells, Molecules, and Diseases 2016
Red blood cells in retinal vascular disorders
R Agrawal, J Sherwood, J Chhablani, A Ricchariya, S Kim, PH Jones, S Balabani, D Shima
Blood Cells, Molecules, and Diseases 2016
In Vivo T1 of Blood Measurements in Children with Sickle Cell Disease Improve Cerebral Blood Flow Quantification from Arterial Spin-Labeling MRI
L Vaclavu, V der Land, DF Heijtel, MJ van Osch, MH Cnossen, CB Majoie, A Bush, JC Wood, KJ Fijnvandraat, HJ Mutsaerts, AJ Nederveen
American Journal of Neuroradiology 2016
Effects of Poloxamer 188 on red blood cell membrane properties in sickle cell anaemia
B Sandor, M Marin, C Lapoumeroulie, M Rabaï, SD Lefevre, N Lemonne, WE Nemer, A Mozar, O Français, BL Pioufle, P Connes, CL van Kim
British Journal of Haematology 2016
Sickle cell disease: challenges and progress
LV Parise, N Berliner
Blood 2016
Micro- and Nanosystems for Biotechnology: Love/Micro- and Nanosystems for Biotechnology
ME Brett, DK Wood
Micro- and Nanosystems for Biotechnology: Love/Micro- and Nanosystems for Biotechnology 2016
Mobility Enhancement of Red Blood Cells with Biopolymers
D Tahara, N Oikawa, R Kurita
Journal of the Physical Society of Japan 2016
Modulation of Sickle Red Blood Cell Adhesion and its Associated Changes in Biomarkers by Sulfated Nonanticoagulant Heparin Derivative
A Alshaiban, V Muralidharan-Chari, A Nepo, SA Mousa
Clinical and Applied Thrombosis/Hemostasis 2016
Sickle Cell Disease
S Azar, TE Wong
Medical Clinics of North America 2016
Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study
R Hierso, N Lemonne, R Villaescusa, ML Lalanne-Mistrih, K Charlot, M Etienne-Julan, B Tressières, Y Lamarre, V Tarer, Y Garnier, AA Hernandez, S Ferracci, P Connes, M Romana, MD Hardy-Dessources
British Journal of Haematology 2016

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 2 patents
96 readers on Mendeley
See more details