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During human thymic development, β 1 integrins regulate adhesion, motility, and the outcome of RHAMM/hyaluronan engagement
Author(s) -
Gares Sheryl L.,
Giannakopoulos Nadia,
MacNeil Donna,
Faull Randall J.,
Pilarski Linda M.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.6.781
Subject(s) - biology , integrin , motility , microbiology and biotechnology , adhesion , hyaluronic acid , cell adhesion , immunology , outcome (game theory) , cell adhesion molecule , cancer research , receptor , anatomy , biochemistry , cell , chemistry , organic chemistry , mathematics , mathematical economics
During human thymic differentiation, interactions between fibronectin (Fn)/β 1 integrins and hyaluronan (HA)/RHAMM control motility and Fn/β 1 integrins mediate spontaneous Fn‐dependent adhesion. Multinegative (MN, CD3 – 4 – 8 – ) thymocytes exhibit strong spontaneous adherence to Fn (75%) that was efficiently inhibited by anti‐α 5 β 1 and only weakly inhibited by anti‐α 4 β 1 . The relatively weak adherence of unfractionated thymocytes to Fn required both α 4 β 1 and α 5 β 1 . Video time‐lapse microscopy indicates that a subset of thymocytes also undergo spontaneous Fn‐dependent motility mediated by α 5 β 1 , α 4 β 1 , and the HA‐receptor RHAMM, but not by CD44. The loss of motility after hyaluronidase treatment of thymocytes indicated that motility is strongly dependent on HA. Of motile cells, 55% were DP, 19% were DN, and 24% were CD4 + SP, but only 1% were CD8 + SP. Overall, for MN thymocytes, β 1 integrin mediated Fn‐adhesion, but after expression of CD4/CD8, β 1 integrins mediated Fn‐dependent motility. Treatment with the activating anti‐β 1 mAb QE.2E5 inhibited thymic motility and converted otherwise nonadherent thymocytes to an adherent state. High‐avidity interactions via integrins appear to supercede the motogenicity of RHAMM and HA, suggesting that integrin avidity may regulate RHAMM. During thymic development, changes in adhesion or motility appear to be mediated by integrin avidity modulation. J. Leukoc. Biol. 64: 781–790; 1998.