Am. Vincent et al., ENDOTHELIAL INTERACTIONS OF HAIRY-CELLS - THE IMPORTANCE OF ALPHA-4-BETA-1 IN THE UNUSUAL TISSUE DISTRIBUTION OF THE DISORDER, Blood, 88(10), 1996, pp. 3945-3952
The tissue-homing of all lymphocytes involves their interactions with
endothelial cells (ECs) and with various tissue accessory cells. Howev
er, in hairy cell leukemia (HCL), these processes are particularly pro
minent and result in diagnostic appearances in the spleen, liver, and
bone marrow. The present study explores the mechanisms that underlie t
hese 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/va
scular cell adhesion molecule-1 (VCAM-1) was established. This recepto
r-ligand pair was shown to be important both for strong adhesion and f
or HC motility/transmigration. A similar importance for alpha 4 beta 1
/VCAM-1 was established for the interaction between HCs and relevant t
issue accessory cells. The in vitro relevance of these findings was co
nfirmed by the demonstration of VCAM-1 in HCL spleen and by the fact t
hat, in frozen sections, HCs adhered (via VCAM-1) to the red pulp, but
not to other areas of normal spleen. These results indicate that alph
a 4 beta 1/VCAM-1 is central to the interaction between HCs and endoth
elium/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 far many of the characteristi
c features of the disease. (C) 1996 by The American Society of Hematol
ogy.