title: Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down-regulation of both L-selectin and CD23.
abstract: Chronic lymphocytic leukaemia (B-CLL) is characterized by a progressive accumulation of B lymphocytes in blood and bone marrow and high concentrations of soluble CD23 and L-selectin are found in the serum of these patients. In this study lymphocytes from normal subjects and patients with B-CLL were allowed to undergo transendothelial migration across confluent layers of human umbilical vein endothelial cells. Lymphocytes in B-CLL samples showed an impaired capacity to migrate while the minor proportion of normal T cells was enriched by a mean of 2.5-fold in the transmigrated lymphocytes. In contrast, the ratio of B to T lymphocytes in normal preparations was unchanged in the transmigrated population. The expression of adhesion molecules on B-CLL lymphocytes before and after transendothelial migration was studied by flow cytometry which showed that 71 +/- 5% of L-selectin was lost from the surface of transmigrated lymphocytes. T and B cells from normal subjects also showed a major loss of L-selectin after transmigration. B-CLL lymphocytes and normal B cells expressed CD23 but this molecule was down-regulated following transendothelial migration, whereas the expression of VLA-4, ICAM-1, LFA-1 and CD44 was unchanged. Lymphocytes incubated with oxidized ATP, an irreversible inhibitor of P2Z/P2X7 purinoceptors, retained their capacity for transendothelial migration and showed the same loss of L-selectin as control leukaemic lymphocytes. Our results show that B-CLL lymphocytes have impaired ability for transendothelial migration compared to normal peripheral blood lymphocytes. Moreover, transendothelial migration involves a universal loss of L-selectin and CD23 from lymphocytes which suggests that the high serum levels of soluble L-selectin and CD23 observed in B-CLL may be generated by shedding during the process of transendothelial migration.
authors.affiliation: Sydney University Department of Medicine, Nepean Hospital, Penrith, N.S.W., Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Chen
authors.forename: B J
authors.initials: BJ
authors.lastname: Gu
authors.forename: L P
authors.initials: LP
authors.lastname: Dao
authors.forename: C J
authors.initials: CJ
authors.lastname: Bradley
authors.forename: S P
authors.initials: SP
authors.lastname: Mulligan
authors.forename: J S
authors.initials: JS
authors.lastname: Wiley
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D015536:Down-Regulation; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*
chemical_list: D017455:Receptors, IgE; D019041:L-Selectin