Growth hormone modulates thymocyte development in vivo through a combined action of laminin and CXC chemokine ligand 12.
Previous evidence indicates that GH modulates thymic cell migration. In this study we approached this issue in vivo, studying thymocyte migration in GH transgenic animals and in normal mice treated intrathymically with GH. Extracellular matrix and chemokines are involved in thymocyte migration. In this respect, thymocyte adhesion to laminin was higher in GH-treated animals than controls, and the numbers of migrating cells in laminin-coated Transwells was higher in GH-transgenic and GH-injected mice. Additionally, CXC chemokine ligand 12 (CXCL12)-driven migration was higher in GH-Tg and GH-treated animals compared with controls. Interestingly, although CXCR4 expression on thymocytes did not change in GH-Tg mice, the CXCL12 intrathymic contents were higher. We found that CXCL12, in conjunction with laminin, would additionally enhance the migration of thymocytes previously exposed to high concentrations of GH in vivo. Lastly, there was an augmentation of recent thymic emigrants in lymph nodes from GH-Tg and GH-injected animals. In conclusion, enhanced thymocyte migration in GH transgenic mice as well as GH-injected mice results at least partially from a combined action of laminin and CXCL12. Considering that GH is presently being used as an adjuvant therapeutic agent in immunodeficiencies, including AIDS, the concepts defined herein provide important background knowledge for future GH-based immune interventions.
Smaniotto
Salete
S
Institut National de la Santé et de la Recherche Médicale/Fiocruz Associate Laboratory of Immunology, Laboratory on Thymus Research, Oswaldo Cruz Institute, 21045-900 Rio de Janeiro, Brazil.
de Mello-Coelho
Valéria
V
Villa-Verde
Déa Maria Serra
DM
Pléau
Jean-Marie
JM
Postel-Vinay
Marie-Catherine
MC
Dardenne
Mireille
M
Savino
Wilson
W
D000818:Animals; D030801:Animals, Genetically Modified; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004357:Drug Synergism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D007267:Injections; D007797:Laminin / Q000494:pharmacology*; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D007797:Laminin; D008024:Ligands; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D013006:Growth Hormone