Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Journal Club
  • Published:

Unclogging sickle cell anaemia

Nature Reviews Molecular Cell Biology volume 18, page 214 (2017)Cite this article

Subjects

In 1949, the molecular basis of a disease was identified for the first time, that of sickle cell anaemia, by Pauling, Itano and colleagues. Since then, generations of students were taught that the substitution of a specific glutamate with valine in the β-globin protein results in polymerization of haemoglobin. This polymerization produces the deformed sickle-shaped red blood cell or 'sickle erythrocyte' that is characteristic of this disease, which affects millions worldwide.

However, this intracellular disease aetiology belies the complex cell surface interactions that orchestrate the pathogenesis of acute sickle cell anaemia. Occlusion of the small blood vessels in sickle cell anaemia is extremely painful and can be life-threatening. The initial event in vaso-occlusion is the reduced passage of sickle erythrocytes through capillaries, but activation of endothelial cells and platelets follows soon after. This leads to adhesion of erythrocytes and leukocytes to the endothelium in the form of multicellular aggregates, and to the amplification of vaso-occlusion — like a multi-vehicle accident blocking a highway.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Pauling, L. et al. Sickle cell anemia, a molecular disease. Science 110, 543–548 (1949)

    Article  CAS  Google Scholar 

  2. Matsui, N. M. et al. P-selectin mediates the adhesion of sickle erythrocytes to the endothelium. Blood https://doi.org/10.1182/blood.V98.6.1955 98, 1955–1962 (2001)

    Article  CAS  Google Scholar 

  3. Ataga, K. I. et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1611770 376, 429–439 (2017)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Cambridge, 02142, MA, USA

    Hojun Li & Harvey Lodish

Authors
  1. Hojun Li
    View author publications

    Search author on:PubMed Google Scholar

  2. Harvey Lodish
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Harvey Lodish.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, H., Lodish, H. Unclogging sickle cell anaemia. Nat Rev Mol Cell Biol 18, 214 (2017). https://doi.org/10.1038/nrm.2017.17

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nrm.2017.17

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing