Molecular pathways in bone marrow homing:: dominant role of α4β1 over β2-integrins and selectins

被引:150
作者
Papayannopoulou, T [1 ]
Priestley, GV [1 ]
Nakamoto, B [1 ]
Zafiropoulos, V [1 ]
Scott, LM [1 ]
机构
[1] Univ Washington, Div Hematol, Seattle, WA 98195 USA
关键词
D O I
10.1182/blood.V98.8.2403
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The specific retention of intravenously administered hemopoietic cells within bone marrow is a complex multistep process. Despite recent insights, the molecular mechanics governing this process remain largely undefined. This study explored the influence of beta (2)-integrins on the homing to bone marrow and repopulation kinetics of progenitor cells. Both antifunctional antibodies and genetically deficient cells were used. In addition, triple selectin-deficient mice were used as recipients of either deficient (selectin or beta (2)) or normal cells in homing experiments. The homing patterns of either beta (2) null or selectin null cells into normal or selectin-deficient recipients were similar to those of normal cells given to normal recipients. Furthermore, spleen colony-forming units and the early bone marrow repopulating activity for the first 2 weeks after transplantation were not significantly different from those of control cells. These data are in contrast to the importance of beta (2)-integrin and selectins in the adhesion/migration cascade of mature leukocytes. The special bone marrow flow hemodynamics may account for these differences. Although early deaths after transplantation can be seen in recipients deficient in CD18 and selectin, these are attributed to septic complications rather than homing defects. However, when beta (2)- or selectin-null donor cells are treated with anti-alpha (4) antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (>90%) was found. The data suggest that the alpha (4)beta (1)/vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within the bone marrow, but if its function is compromised, the synergistic contribution of other pathways, that is, beta (2)-integrins or selectins, is uncovered. (C) 2001 by The American Society of Hematology.
引用
收藏
页码:2403 / 2411
页数:9
相关论文
共 73 条
[1]  
Abe Y, 1996, J IMMUNOL, V157, P5061
[2]   THE INTEGRIN VLA-4 SUPPORTS TETHERING AND ROLLING IN FLOW ON VCAM-1 [J].
ALON, R ;
KASSNER, PD ;
CARR, MW ;
FINGER, EB ;
HEMLER, ME ;
SPRINGER, TA .
JOURNAL OF CELL BIOLOGY, 1995, 128 (06) :1243-1253
[3]   α4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo [J].
Arroyo, AG ;
Yang, JT ;
Rayburn, H ;
Hynes, RO .
IMMUNITY, 1999, 11 (05) :555-566
[4]   In vivo roles of integrins during leukocyte development and traffic:: Insights from the analysis of mice chimeric for α5, αv, and α4 integrins [J].
Arroyo, AG ;
Taverna, D ;
Whittaker, CA ;
Strauch, UG ;
Bader, BL ;
Rayburn, H ;
Crowley, D ;
Parker, CM ;
Hynes, RO .
JOURNAL OF IMMUNOLOGY, 2000, 165 (08) :4667-4675
[5]   ALPHA-4 INTEGRINS MEDIATE LYMPHOCYTE ATTACHMENT AND ROLLING UNDER PHYSIOLOGICAL FLOW [J].
BERLIN, C ;
BARGATZE, RF ;
CAMPBELL, JJ ;
VONANDRIAN, UH ;
SZABO, MC ;
HASSLEN, SR ;
NELSON, RD ;
BERG, EL ;
ERLANDSEN, SL ;
BUTCHER, EC .
CELL, 1995, 80 (03) :413-422
[6]   Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice [J].
Berlin-Rufenach, C ;
Otto, F ;
Mathies, M ;
Westermann, J ;
Owen, MJ ;
Hamann, A ;
Hogg, N .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (09) :1467-1478
[7]   The role of α4 and LFA-1 integrins in selectin-independent monocyte and neutrophil migration to joints of rats with adjuvant arthritis [J].
Birner, U ;
Issekutz, TB ;
Walter, U ;
Issekutz, AC .
INTERNATIONAL IMMUNOLOGY, 2000, 12 (02) :141-150
[9]   Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers [J].
Bradstock, KF ;
Makrynikola, V ;
Bianchi, A ;
Shen, W ;
Hewson, J ;
Gottlieb, DJ .
LEUKEMIA, 2000, 14 (05) :882-888
[10]   Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1-and CD106 (VCAM-1)-dependent mechanism [J].
Burger, JA ;
Zvaifler, NJ ;
Tsukada, N ;
Firestein, GS ;
Kipps, TJ .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :305-315