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Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down‐regulation of both L‐selectin and CD23
Author(s) -
Chen Joan,
Gu Ben,
Dao LanPhuong,
Bradley Christopher,
Mulligan Stephen,
Wiley James
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1999.01278.x
Subject(s) - l selectin , cd44 , lymphocyte , population , chronic lymphocytic leukemia , biology , immunology , cd23 , cd38 , endothelium , bone marrow , flow cytometry , cell adhesion molecule , microbiology and biotechnology , chemistry , leukemia , medicine , in vitro , endocrinology , antibody , immunoglobulin e , biochemistry , environmental health , stem cell , cd34
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.