Endothelial interactions of hairy cells: the importance of alpha 4 beta 1 in the unusual tissue distribution of the disorder.
The tissue-homing of all lymphocytes involves their interactions with endothelial cells (ECs) and with various tissue accessory cells. However, in hairy cell leukemia (HCL), these processes are particularly prominent and result in diagnostic appearances in the spleen, liver, and bone marrow. The present study explores the mechanisms that underlie these tissue reactions. Using a human umbilical vein EC (HUVEC) model, various possible receptor-ligand interactions between hairy cells (HCs) and ECs were examined and a central importance for alpha 4 beta 1/vascular cell adhesion molecule-1 (VCAM-1) was established. This receptor-ligand pair was shown to be important both for strong adhesion and for HC motility/transmigration. A similar importance for alpha 4 beta 1/VCAM-1 was established for the interaction between HCs and relevant tissue accessory cells. The in vitro relevance of these findings was confirmed by the demonstration of VCAM-1 in HCL spleen and by the fact that, in frozen sections, HCs adhered (via VCAM-1) to the red pulp, but not to other areas of normal spleen. These results indicate that alpha 4 beta 1/VCAM-1 is central to the interaction between HCs and endothelium/accessory cells. Such interactions, together with the intrinsic cell activation characteristic of HCL and the HC's consequent ability to interact with matrix, are responsible for many of the characteristic features of the disease.
Department of Haematology, Royal Liverpool University Hospital, UK.
A M
AM
Vincent
J
J
Burthem
R
R
Brew
J C
JC
Cawley
D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007943:Leukemia, Hairy Cell / Q000473:pathology*; D008024:Ligands; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013154:Spleen / Q000473:pathology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D039041:Integrin alpha4beta1; D016023:Integrins; D008024:Ligands; D009363:Neoplasm Proteins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1