PMID- 15802502 OWN - NLM STAT- MEDLINE DCOM- 20050721 LR - 20071115 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 146 IP - 7 DP - 2005 Jul TI - Growth hormone modulates thymocyte development in vivo through a combined action of laminin and CXC chemokine ligand 12. PG - 3005-17 AB - 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. FAU - Smaniotto, Salete AU - Smaniotto S AD - Institut National de la Sante et de la Recherche Medicale/Fiocruz Associate Laboratory of Immunology, Laboratory on Thymus Research, Oswaldo Cruz Institute, 21045-900 Rio de Janeiro, Brazil. FAU - de Mello-Coelho, Valeria AU - de Mello-Coelho V FAU - Villa-Verde, Dea Maria Serra AU - Villa-Verde DM FAU - Pleau, Jean-Marie AU - Pleau JM FAU - Postel-Vinay, Marie-Catherine AU - Postel-Vinay MC FAU - Dardenne, Mireille AU - Dardenne M FAU - Savino, Wilson AU - Savino W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050331 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (Cxcl12 protein, mouse) RN - 0 (Laminin) RN - 0 (Ligands) RN - 0 (Receptors, Cell Surface) RN - 0 (Recombinant Proteins) RN - 9002-72-6 (Growth Hormone) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Cattle MH - Cell Adhesion/drug effects MH - Cell Movement/drug effects MH - Chemokine CXCL12 MH - Chemokines, CXC/*pharmacology MH - Drug Synergism MH - Extracellular Matrix/metabolism MH - Female MH - Growth Hormone/administration & dosage/genetics/*pharmacology MH - Injections MH - Laminin/*pharmacology MH - Ligands MH - Lymph Nodes/cytology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Receptors, Cell Surface/metabolism MH - Recombinant Proteins/administration & dosage/pharmacology MH - Thymus Gland/*cytology/drug effects/*physiology EDAT- 2005/04/02 09:00 MHDA- 2005/07/22 09:00 CRDT- 2005/04/02 09:00 PHST- 2005/04/02 09:00 [pubmed] PHST- 2005/07/22 09:00 [medline] PHST- 2005/04/02 09:00 [entrez] AID - en.2004-0709 [pii] AID - 10.1210/en.2004-0709 [doi] PST - ppublish SO - Endocrinology. 2005 Jul;146(7):3005-17. doi: 10.1210/en.2004-0709. Epub 2005 Mar 31.