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.
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.
Patrick
C W
CW
Department of Internal Medicine, University of Texas Health Science Center at Houston 77030.
Juneja
H S
HS
Lee
S
S
Schmalstieg
F C
FC
McIntire
L V
LV
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology; D002465:Cell Movement; D002860:Chromium Radioisotopes; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D039001:Integrin alpha Chains; D039441:Integrin alpha4; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000276:immunology / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; C063493:CDw49d; D015815:Cell Adhesion Molecules; D002860:Chromium Radioisotopes; D039001:Integrin alpha Chains; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4