Enhanced adherence of sickle erythrocytes to thrombin-treated endothelial cells involves interendothelial cell gap formation.
The adherence of sickle erythrocytes to vascular endothelium has the capacity to initiate vasoocclusion. The known effects of thrombin on endothelial cell function and the increased activity of thrombin in sickle cell disease led us to examine the effect of thrombin on the adhesivity of cultured endothelial cells for sickle erythrocytes. In particular, we studied whether the effect of thrombin on interendothelial cell gap formation (ICGF) was involved in endothelial cell adhesivity for sickle erythrocytes. Those endothelial cell monolayers stimulated by thrombin to maximal levels of static sickle erythrocyte adherence also underwent striking cell contraction and enlargement of interendothelial cell gaps. Adhesivity also increased when gaps were induced with antilaminin antibodies or EDTA. Maximally adhesogenic thrombin conditions failed to increase adhesivity when gap formation was prevented by pretreatment of the monolayers with 8-bromo-cyclic adenosine monophosphate (bromo-cAMP) or glutaraldehyde, agents that respectively inhibit actin-myosin-dependent cell contraction or cross-link adjacent cells in the monolayer. The influence of these two agents on EDTA-enhanced adhesivity was linked to their ability to prevent gap formation. Glutaraldehyde prevented both increased adherence and gap formation; bromo-cAMP prevented neither. Interendothelial cell gap formation may contribute to vasoocclusion by facilitating sickle erythrocyte adherence.
Manodori
A B
AB
Hematology Division, the Department of Medicine, The University of California, San Francisco, USA.
Matsui
N M
NM
Chen
J Y
JY
Embury
S H
SH
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000755:Anemia, Sickle Cell / Q000150:complications / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology*; D005976:Glutaral / Q000494:pharmacology; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology; D007797:Laminin / Q000276:immunology / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D007797:Laminin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004492:Edetic Acid; D013917:Thrombin; D005976:Glutaral