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This version published online on March 31, 2005
Endocrinology, doi:10.1210/en.2004-0709
A more recent version of this article appeared on July 1, 2005
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Submitted on June 7, 2004
Accepted on November 11, 2004

Growth hormone modulates thymocyte development in vivo through a combined action of laminin and CXCL12

Salete Smaniotto, Valéria de Mello-Coelho, Déa Maria Serra Villa-Verde, Jean-Marie Pléau, Marie-Catherine Postel-Vinay, Mireille Dardenne, and Wilson Savino*

Inserm/Fiocruz Associate Laboratory of Immunology, Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Department of Morphology, Federal University of Alagoas, Maceió, Brazil; Hôpital Necker, UMR 8147, Paris, France; National Institute of Aging, NIH, Baltimore, USA; Hôpital Necker, Inserm U-344, Paris, France

* To whom correspondence should be addressed. E-mail: savino{at}fiocruz.br.

Previous evidence indicates that growth hormone (GH) modulates thymic cell migration. Here, 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, 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 further enhance 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.


Key words: Growth Hormone • Thymus • Cell Migration




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