Role and regulation of sickle red cell interactions with other cells: ICAM-4 and other adhesion receptors.
Erythrocytes containing primarily hemoglobin S (SS RBCs) are abnormally adherent. We now know that SS RBCs express numerous adhesion molecules, and that many of these can undergo activation. SS RBCs exposed briefly to epinephrine show markedly increased adhesion to both laminin and endothelial cells. In vivo, infusion of epinephrine-activated but not unstimulated SS RBCs causes RBC adhesion, vaso-occlusion, organ trapping, and shortened RBC survival in the circulation. Epinephrine treatment of SS RBCs before infusion also induces adhesion of murine leukocytes to vascular walls. Indeed, in vitro, SS RBCs can activate leukocyte adhesion and cytokine production. We now have demonstrated both in vitro and in vivo evidence for the importance of RBC signaling and have also shown that SS RBC adhesion is determined by genetic polymorphisms in the signaling pathway that activates adhesion. These advances will hopefully lead to new therapeutic modalities for sickle cell disease.
Zennadi
R
R
Department of Medicine and Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC 27710, USA.
De Castro
L
L
Eyler
C
C
Xu
K
K
Ko
M
M
Telen
M J
MJ
D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D011110:Polymorphism, Genetic; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; C095100:ICAM4 protein, human; D007797:Laminin