Development and characterization of a physiologically relevant model of lymphocyte migration in chronic lymphocytic leukemia.

Abstract:

:There is growing evidence that lymphocyte trafficking contributes to the clinical course of chronic lymphocytic leukemia (CLL), but to date, only static in vitro cultures have been used to study these phenomena. To address this lack of data, we have developed a dynamic in vitro model in which CLL cells experience shear forces equivalent to those in capillary beds and are made to flow through capillary-like hollow fibers lined with endothelial cells. CLL cells treated in this way increased their expression of CD62L and CXCR4 (both P < .0001) and of CD49d and CD5 (both P = .003) directly as a result of the shear force. Furthermore, CLL cells migrated through the endothelium into the "extravascular" space (mean migration, 1.37% ± 2.14%; n = 21). Migrated CLL cells had significantly higher expression of CD49d (P = .02), matrix metallopeptidase-9 (P = .004), CD38 (P = .009), CD80 (P = .04), and CD69 (P = .04) compared with CLL cells that remained in the circulation. The degree of migration observed strongly correlated with CD49d expression (r(2), 0.47; P = .01), and treatment with the CD49d-blocking antibody natalizumab resulted in significantly decreased migration (P = .01). Taken together, our data provide evidence for a novel, dynamic, and tractable in vitro model of lymphocyte migration and confirm that CD49d is a critical regulator of this process in CLL.

journal_name

Blood

journal_title

Blood

authors

Walsby E,Buggins A,Devereux S,Jones C,Pratt G,Brennan P,Fegan C,Pepper C

doi

10.1182/blood-2013-12-544569

subject

Has Abstract

pub_date

2014-06-05 00:00:00

pages

3607-17

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2013-12-544569

journal_volume

123

pub_type

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