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Regulation of T ‐lymphocyte motility, adhesion and de‐adhesion by a cell surface mechanism directed by low density lipoprotein receptor‐related protein 1 and endogenous thrombospondin‐1
Author(s) -
Talme Toomas,
Bergdahl Eva,
Sundqvist KarlGösta
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12229
Subject(s) - lrp1 , microbiology and biotechnology , motility , cell adhesion , cell adhesion molecule , integrin , lymphocyte homing receptor , thrombospondins , chemistry , neural cell adhesion molecule , cd47 , biology , receptor , ldl receptor , cell , biochemistry , thrombospondin , lipoprotein , phagocytosis , metalloproteinase , cholesterol , matrix metalloproteinase
Summary T lymphocytes are highly motile and constantly reposition themselves between a free‐floating vascular state, transient adhesion and migration in tissues. The regulation behind this unique dynamic behaviour remains unclear. Here we show that T cells have a cell surface mechanism for integrated regulation of motility and adhesion and that integrin ligands and CXCL 12/ SDF ‐1 influence motility and adhesion through this mechanism. Targeting cell surface‐expressed low‐density lipoprotein receptor‐related protein 1 ( LRP 1) with an antibody, or blocking transport of LRP 1 to the cell surface, perturbed the cell surface distribution of endogenous thrombospondin‐1 ( TSP ‐1) while inhibiting motility and potentiating cytoplasmic spreading on intercellular adhesion molecule 1 ( ICAM ‐1) and fibronectin. Integrin ligands and CXCL 12 stimulated motility and enhanced cell surface expression of LRP 1, intact TSP ‐1 and a 130 000 MW TSP ‐1 fragment while preventing formation of a de‐adhesion‐coupled 110 000 MW TSP ‐1 fragment. The appearance of the 130 000 MW TSP ‐1 fragment was inhibited by the antibody that targeted LRP 1 expression, inhibited motility and enhanced spreading. The TSP ‐1 binding site in the LRP 1‐associated protein, calreticulin, stimulated adhesion to ICAM ‐1 through intact TSP ‐1 and CD 47. Shear flow enhanced cell surface expression of intact TSP ‐1. Hence, chemokines and integrin ligands up‐regulate a dominant motogenic pathway through LRP 1 and TSP ‐1 cleavage and activate an associated adhesion pathway through the LRP 1–calreticulin complex, intact TSP ‐1 and CD 47. This regulation of T ‐cell motility and adhesion makes pro‐adhesive stimuli favour motile responses, which may explain why T cells prioritize movement before permanent adhesion.