Leukocytes in the vaso-occlusive process

Dachuan Zhang, Paul S. Frenette

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Sickle cell disease (SCD) results from a single mutation in the β-globin gene, leading to clinical manifestations that extend far beyond the mutated hemoglobin in red blood cells (RBCs). SCD is associated with a chronic infl ammatory condition that, in the presence of a “second hit”, can produce vaso-occlusive crises (VOC), the major cause of morbidity and mortality of the disease. Leukocytes play an important role in the vaso-occlusive phenomenon, as suggested initially by the fi ndings of clinical studies that high leukocyte count strongly correlates with clinical severity of the disease. Further, intravital microscopy studies in SCD mice have revealed that sickle RBCs directly interact with adherent neutrophils in post- capillary and collecting venules. These heterotypic interactions are mediated by activated α M β 2 (Mac-1) integrin polarized on the leading edge of adherent neutrophils, resulting in severe VOC. A multistep and multicellular model for the vaso- occlusive process is proposed in which endothelial cells are activated by sickle RBCs and multiple infl ammatory mediators, leading to the recruitment of adherent leukocytes. The recruited adherent neutrophils capture circulating sickle RBCs, resulting in reduced blood fl ow and vascular occlusion in the microcirculation. This model has triggered several clinical trials targeting drivers of vaso-occlusion, and suggests a major contribution of leukocytes to sickle cell VOC.

Original languageEnglish (US)
Title of host publicationSickle Cell Anemia: From Basic Science to Clinical Practice
PublisherSpringer International Publishing
Pages91-108
Number of pages18
ISBN (Electronic)9783319067131
ISBN (Print)9783319067124
DOIs
StatePublished - Jan 1 2016

Fingerprint

Sickle Cell Anemia
Leukocytes
Blood
Erythrocytes
Neutrophils
Globins
Venules
Microcirculation
Leukocyte Count
Integrins
Endothelial cells
Blood Vessels
Hemoglobins
Endothelial Cells
Clinical Trials
Morbidity
Mutation
Genes
Cells
Mortality

Keywords

  • Adherent leukocyte
  • Heterotypic interaction
  • Vaso-occlusion
  • Vasoocclusion

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zhang, D., & Frenette, P. S. (2016). Leukocytes in the vaso-occlusive process. In Sickle Cell Anemia: From Basic Science to Clinical Practice (pp. 91-108). Springer International Publishing. https://doi.org/10.1007/978-3-319-06713-1_5

Leukocytes in the vaso-occlusive process. / Zhang, Dachuan; Frenette, Paul S.

Sickle Cell Anemia: From Basic Science to Clinical Practice. Springer International Publishing, 2016. p. 91-108.

Research output: Chapter in Book/Report/Conference proceedingChapter

Zhang, D & Frenette, PS 2016, Leukocytes in the vaso-occlusive process. in Sickle Cell Anemia: From Basic Science to Clinical Practice. Springer International Publishing, pp. 91-108. https://doi.org/10.1007/978-3-319-06713-1_5
Zhang D, Frenette PS. Leukocytes in the vaso-occlusive process. In Sickle Cell Anemia: From Basic Science to Clinical Practice. Springer International Publishing. 2016. p. 91-108 https://doi.org/10.1007/978-3-319-06713-1_5
Zhang, Dachuan ; Frenette, Paul S. / Leukocytes in the vaso-occlusive process. Sickle Cell Anemia: From Basic Science to Clinical Practice. Springer International Publishing, 2016. pp. 91-108
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