Work

Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm

Year: 2002

Type: article

Abstract: Vascular occlusion is the major cause of morbidity and mortality in sickle cell disease but its mechanisms are poorly understood. We demonstrate by using intravital microscopy in mice expressing human sickle hemoglobin (SS) that SS red blood cells (RBCs) bind to adherent leukocytes in inflamed venules, producing vasoocclusion of cremasteric venules. SS mice deficient in P- and E-selectins, which display defective leukocyte recruitment to the vessel wall, are protected from vasoocclusion. These data uncover a previously unsuspected paradigm for the pathogenesis of sickle cell vasoocclusion in which adherent leukocytes play a direct role and suggest that drugs targeting SS RBC-leukocyte or leukocyte-endothelial interactions may prevent or treat the vascular complications of this debilitating disease.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.052522799

Authors: Aslihan Turhan, Linnea A. Weiss, Narla Mohandas, Barry S. Coller, Paul S. Frenette

Institutions: Icahn School of Medicine at Mount Sinai, Rockefeller University

Language: English

Topic: Hemoglobinopathies and Related Disorders

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases