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Heterotypic adherence between human B-lymphoblastic and pre-B-
lymphoblastic cells and marrow stromal cells is a biphasic event: integrin
very late antigen-4 alpha mediates only the early phase of the heterotypic
adhesion
CW Patrick , HS Juneja, S Lee, FC Schmalstieg and LV McIntire
Department of Internal Medicine, University of Texas Health Science Center
at Houston 77030.
Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic
cells is essential for normal lymphopoiesis and malignant lymphoblastic
development. However, the detailed molecular mechanisms by which this
heterotypic adherence occurs are poorly understood. The cell-cell
interactions between a B-lymphoblastic cell line (UTMB-460) and a
pre-B-cell line (NALM-6) with MSC were chosen as models to investigate
potential mechanisms and adhesion molecules involved in the apposition
between normal and malignant lymphoblastic cells and MSC. A parallel-flow
detachment assay (PFDA) and a 51Cr detachment assay, coupled with
monoclonal antibody (MoAb) blocking experiments, were used to quantify the
attachment of lymphoblastic cells to confluent monolayers of MSC. The
apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was
investigated for variable time periods, ranging from 1 minute to 4 hours.
Results from the temporal study suggest that the heterotypic adherence of
the B-lymphoblastic cells to MSC is a biphasic event and the interactions
occur rapidly (< or = 1 minute) after the two cells come into contact.
More specifically, the early phase of adherence (< or = 15 minutes)
solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell
adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly
complete inhibition (93%) of UTMB-460 cell adherence in the presence of
anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite
the continuous presence of anti-VLA-4 alpha. In addition, the late-phase
adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or
L-selectin, which suggests the possible involvement of other adhesion
molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also
biphasic. Integrin VLA-4 is again a major player in the early phase of
pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may
be important in homing of the malignant lymphoblastic cells to the MSC and
the late phase in retention of malignant lymphoblastic cells in the bone
marrow.
Volume 85,
Issue 1,
pp. 168-178,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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