Cytokines in sickle cell disease

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Sickle red cells express adhesion molecules including integrin α 4β 1, CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD36 and integrins leading to its activation. Monocytes also activate endothelium by releasing proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β). Sickle monocytes also express increased surface CD11b and cytoplasmic cytokines TNFα and IL-1β indicating activated state. Polymorphonuclear leukocytes (PMNs) are also activated with reduced L-selectin expression, enhanced CD64 expression and elevated levels of sL-selectin, sCD16 and elastase resulting in increased adhesiveness to the endothelium. Platelets are also activated and secrete thrombospondin (TSP) and cytokine IL-1. They also form platelet- monocytes aggregates causing endothelial cell P-selectin expression. Endothelial cell activation by these multiple mechanisms leads to a loss of vascular integrity, expression of leukocyte adhesion molecules, change in the surface phenotype from antithrombotic to prothrombotic, excessive cytokine production and upregulation of HLA molecules. Furthermore, contraction of these activated endothelial cells leads to exposure of extracellular matrix proteins, such as TSP, laminin, and fibronectin and their participation in adhesive interactions with bridging molecules from the plasma such as von Willebrand factor (vWf) released from endothelial cells, ultimately culminating in vasoocclusion and local tissue ischemia, the pathognomonic basis of vasoocclusive crisis.

Original languageEnglish
Pages (from-to)329-337
Number of pages9
JournalHematology
Volume8
Issue number5
Publication statusPublished - Oct 2003

Fingerprint

Sickle Cell Anemia
Endothelial Cells
Cytokines
Interleukin-1
Integrins
Thrombospondins
Monocytes
P-Selectin
Cell Adhesion Molecules
Endothelium
Blood Platelets
Erythrocyte Anion Exchange Protein 1
L-Selectin
Selectins
Adhesiveness
E-Selectin
Vascular Cell Adhesion Molecule-1
Extracellular Matrix Proteins
Pancreatic Elastase
Phosphatidylserines

Keywords

  • Cytokines
  • Polmorphonuclear leukocytes
  • Sickle cell disease
  • Vasoocclusion

ASJC Scopus subject areas

  • Hematology

Cite this

Cytokines in sickle cell disease. / Pathare, Anil; Al Kindi, Salam; Daar, Shahina; Dennison, David.

In: Hematology, Vol. 8, No. 5, 10.2003, p. 329-337.

Research output: Contribution to journalArticle

Pathare, Anil ; Al Kindi, Salam ; Daar, Shahina ; Dennison, David. / Cytokines in sickle cell disease. In: Hematology. 2003 ; Vol. 8, No. 5. pp. 329-337.
@article{26c0906e147b4b8f8296976e5c06f1e2,
title = "Cytokines in sickle cell disease",
abstract = "Sickle red cells express adhesion molecules including integrin α 4β 1, CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD36 and integrins leading to its activation. Monocytes also activate endothelium by releasing proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β). Sickle monocytes also express increased surface CD11b and cytoplasmic cytokines TNFα and IL-1β indicating activated state. Polymorphonuclear leukocytes (PMNs) are also activated with reduced L-selectin expression, enhanced CD64 expression and elevated levels of sL-selectin, sCD16 and elastase resulting in increased adhesiveness to the endothelium. Platelets are also activated and secrete thrombospondin (TSP) and cytokine IL-1. They also form platelet- monocytes aggregates causing endothelial cell P-selectin expression. Endothelial cell activation by these multiple mechanisms leads to a loss of vascular integrity, expression of leukocyte adhesion molecules, change in the surface phenotype from antithrombotic to prothrombotic, excessive cytokine production and upregulation of HLA molecules. Furthermore, contraction of these activated endothelial cells leads to exposure of extracellular matrix proteins, such as TSP, laminin, and fibronectin and their participation in adhesive interactions with bridging molecules from the plasma such as von Willebrand factor (vWf) released from endothelial cells, ultimately culminating in vasoocclusion and local tissue ischemia, the pathognomonic basis of vasoocclusive crisis.",
keywords = "Cytokines, Polmorphonuclear leukocytes, Sickle cell disease, Vasoocclusion",
author = "Anil Pathare and {Al Kindi}, Salam and Shahina Daar and David Dennison",
year = "2003",
month = "10",
language = "English",
volume = "8",
pages = "329--337",
journal = "Hematology",
issn = "1024-5332",
publisher = "Taylor and Francis Ltd.",
number = "5",

}

TY - JOUR

T1 - Cytokines in sickle cell disease

AU - Pathare, Anil

AU - Al Kindi, Salam

AU - Daar, Shahina

AU - Dennison, David

PY - 2003/10

Y1 - 2003/10

N2 - Sickle red cells express adhesion molecules including integrin α 4β 1, CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD36 and integrins leading to its activation. Monocytes also activate endothelium by releasing proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β). Sickle monocytes also express increased surface CD11b and cytoplasmic cytokines TNFα and IL-1β indicating activated state. Polymorphonuclear leukocytes (PMNs) are also activated with reduced L-selectin expression, enhanced CD64 expression and elevated levels of sL-selectin, sCD16 and elastase resulting in increased adhesiveness to the endothelium. Platelets are also activated and secrete thrombospondin (TSP) and cytokine IL-1. They also form platelet- monocytes aggregates causing endothelial cell P-selectin expression. Endothelial cell activation by these multiple mechanisms leads to a loss of vascular integrity, expression of leukocyte adhesion molecules, change in the surface phenotype from antithrombotic to prothrombotic, excessive cytokine production and upregulation of HLA molecules. Furthermore, contraction of these activated endothelial cells leads to exposure of extracellular matrix proteins, such as TSP, laminin, and fibronectin and their participation in adhesive interactions with bridging molecules from the plasma such as von Willebrand factor (vWf) released from endothelial cells, ultimately culminating in vasoocclusion and local tissue ischemia, the pathognomonic basis of vasoocclusive crisis.

AB - Sickle red cells express adhesion molecules including integrin α 4β 1, CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD36 and integrins leading to its activation. Monocytes also activate endothelium by releasing proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β). Sickle monocytes also express increased surface CD11b and cytoplasmic cytokines TNFα and IL-1β indicating activated state. Polymorphonuclear leukocytes (PMNs) are also activated with reduced L-selectin expression, enhanced CD64 expression and elevated levels of sL-selectin, sCD16 and elastase resulting in increased adhesiveness to the endothelium. Platelets are also activated and secrete thrombospondin (TSP) and cytokine IL-1. They also form platelet- monocytes aggregates causing endothelial cell P-selectin expression. Endothelial cell activation by these multiple mechanisms leads to a loss of vascular integrity, expression of leukocyte adhesion molecules, change in the surface phenotype from antithrombotic to prothrombotic, excessive cytokine production and upregulation of HLA molecules. Furthermore, contraction of these activated endothelial cells leads to exposure of extracellular matrix proteins, such as TSP, laminin, and fibronectin and their participation in adhesive interactions with bridging molecules from the plasma such as von Willebrand factor (vWf) released from endothelial cells, ultimately culminating in vasoocclusion and local tissue ischemia, the pathognomonic basis of vasoocclusive crisis.

KW - Cytokines

KW - Polmorphonuclear leukocytes

KW - Sickle cell disease

KW - Vasoocclusion

UR - http://www.scopus.com/inward/record.url?scp=0142211186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142211186&partnerID=8YFLogxK

M3 - Article

C2 - 14530175

AN - SCOPUS:0142211186

VL - 8

SP - 329

EP - 337

JO - Hematology

JF - Hematology

SN - 1024-5332

IS - 5

ER -