Journal article
Factor H interferes with the adhesion of sickle red cells to vascular endothelium: a novel disease-modulating molecule.
- Lombardi E Department of Translational Research, National Cancer Center, Aviano, Italy.
- Matte A Department of Medicine, University of Verona-AOUI Verona; Italy.
- Risitano AM Hematology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
- Ricklin D Molecular Pharmacy Group, Department of Pharmaceutical Sciences, University of Basel, Switzerland.
- Lambris JD Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; USA.
- De Zanet D Department of Translational Research, National Cancer Center, Aviano, Italy.
- Jokiranta ST Research Programs Unit, Immunobiology, University of Helsinki and United Medix Laboratories, Helsinki, Finland.
- Martinelli N Department of Medicine, University of Verona-AOUI Verona; Italy.
- Scambi C Department of Medicine, University of Verona-AOUI Verona; Italy.
- Salvagno G Laboratory of Clinical Biochemistry, Department of Life and Reproduction Sciences, University of Verona, Italy.
- Bisoffi Z Centre of Tropical Diseases, Sacro Cuore-Don Calabria Hospital Negrar, Verona, Italy.
- Colato C Department of Diagnostics and Public Health, University of Verona-AOUI Verona, Italy.
- Siciliano A Department of Medicine, University of Verona-AOUI Verona; Italy.
- Bortolami O Unit of Epidemiology and Medical Statistics, Department of Diagnostic & Public Health, University of Verona.
- Mazzuccato M Department of Translational Research, National Cancer Center, Aviano, Italy.
- Zorzi F Department of Medicine, University of Verona-AOUI Verona; Italy.
- De Marco L Department of Translational Research, National Cancer Center, Aviano, Italy.
- De Franceschi L Department of Medicine, University of Verona-AOUI Verona; Italy lucia.defranceschi@univr.it.
- 2019-01-12
Published in:
- Haematologica. - 2019
Adolescent
Adult
Anemia, Sickle Cell
Case-Control Studies
Cell Adhesion
Cell Communication
Cells, Cultured
Complement Factor H
Complement Membrane Attack Complex
Endothelium, Vascular
Erythrocytes
Erythrocytes, Abnormal
Female
Follow-Up Studies
Humans
Macrophage-1 Antigen
Male
Middle Aged
P-Selectin
Young Adult
English
Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar "stop-and-go" motion of sickle cell red blood cells on tumor factor-α-activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor Has an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.3324/haematol.2018.198622
- PMID 30630982
- Persistent URL
- https://sonar.ch/global/documents/232491
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