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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2578-2586.
Prepublished online as a Blood First Edition Paper on July 6, 2006; DOI 10.1182/blood-2005-12-010827.


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HEMATOPOIESIS

CD99 expressed on human mobilized peripheral blood CD34+ cells is involved in transendothelial migration

Anne-Marie Imbert, Ghania Belaaloui, Florence Bardin, Cecile Tonnelle, Marc Lopez, and Christian Chabannon

From the Centre de Thérapie Cellulaire et Génique, Institut Paoli-Calmettes; Centre Régional de Lutte Contre le Cancer Provence-Alpes-Côte d'Azur; and Equipe d'Hématopoïèse Moléculaire et Fonctionnelle, Unité Mixte de Recherche (UMR) 599 Institut National de la Santé et de la Recherche Médicale (Inserm)-Centre Régional de Lutte contre le Cancer (CRLCC)-Université de la Méditerranée, Centre de Recherche en Cancérologie de Marseille, France.

Hematopoietic progenitor cell trafficking is an important phenomenon throughout life. It is thought to occur in sequential steps, similar to what has been described for mature leukocytes. Molecular actors have been identified for each step of leukocyte migration; recently, CD99 was shown to play a part during transendothelial migration. We explored the expression and role of CD99 on human hematopoietic progenitors. We demonstrate that (1) CD34+ cells express CD99, albeit with various intensities; (2) subsets of CD34+ cells with high or low levels of CD99 expression produce different numbers of erythroid, natural killer (NK), or dendritic cells in the in vitro differentiation assays; (3) the level of CD99 expression is related to the ability to differentiate toward B cells; (4) CD34+ cells that migrate through an endothelial monolayer in response to SDF-1{alpha} and SCF display the highest level of CD99 expression; (5) binding of a neutralizing antibody to CD99 partially inhibits transendothelial migration of CD34+ progenitors in an in vitro assay; and (6) binding of a neutralizing antibody to CD99 reduces homing of CD34+ progenitors xenotransplanted in NOD-SCID mice. We conclude that expression of CD99 on human CD34+ progenitors has functional significance and that CD99 may be involved in transendothelial migration of progenitors.


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