Mature human thymocytes migrate on laminin-5 with activation of metalloproteinase-14 and cleavage of CD44.
We have previously shown that laminin-5 is expressed in the human thymic medulla, in which mature thymocytes are located. We now report that laminin-5 promotes migration of mature medullary thymocytes, whereas it has no effect on cortical immature thymocytes. Migration was inhibited by blocking mAbs directed against laminin-5 integrin receptors and by inhibitors of metalloproteinases. Interactions of thymocytes with laminin-5 induced a strong up-regulation of active metalloproteinase-14. However, we found that thymocytes did not cleave the laminin-5 gamma(2) chain, suggesting that they do not use the same pathway as epithelial cells to migrate on laminin-5. Interactions of thymocytes with laminin-5 also induced the release of a soluble fragment of CD44 cell surface molecule. Moreover, CD44-rich supernatants induced thymocyte migration in contrast with supernatants depleted in CD44 by immunoadsorption. CD44 cleavage was recently reported to be due to metalloproteinase-14 activation and led to increased migration in cancer cells. Thus, in this study, we show that laminin-5 promotes human mature thymocyte migration in vitro via a multimolecular mechanism involving laminin-5 integrin receptors, metalloproteinase-14 and CD44. These data suggest that, in vivo, laminin-5 may function in the migration of mature thymocytes within the medulla and be part of the thymic emigration process.
Vivinus-Nebot
Mylène
M
Institut National de la Santé et de la Recherche Médicale, Unité 576, Nice, France.
Rousselle
Patricia
P
Breittmayer
Jean-Philippe
JP
Cenciarini
Claire
C
Berrih-Aknin
Sonia
S
Spong
Suzanne
S
Nokelainen
Pasi
P
Cottrez
Françoise
F
Marinkovich
M Peter
MP
Bernard
Alain
A
D015815:Cell Adhesion Molecules / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism* / Q000502:physiology; D006868:Hydrolysis; D016130:Immunophenotyping; D007223:Infant; D039201:Integrin alpha3beta1 / Q000502:physiology; D039161:Integrin alpha6beta4 / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D021122:Protein Subunits / Q000378:metabolism; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D010446:Peptide Fragments; D021122:Protein Subunits; D000097794:Kalinin; C400567:LAMC2 protein, human