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Progesterone reduces the migration of mast cells toward the chemokine stromal cell-derived factor-1/CXCL12 with an accompanying decrease in CXCR4 receptors

¹Institut National de la Santé et de la Recherche Médicale, Univ Paris-Sud 11, Institut Fédératif de Recherche 13, Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Microbiologie-Immunologie Biologique, Clamart; ²Institut Supérieur d'Agriculture de Beauvais, Beauvais; ³Institut National de la Recherche Agronomique, Laboratoire de Nutrition et de Sécurité alimentaire, Jouy en Josas; and ⁴Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Biochimie, Hôpital Antoine Béclère, Clamart, France

Submitted 16 June 2006 ; accepted in final form 12 January 2007

Mast cell recruitment is implicated in many physiological functions and several diseases. It depends on microenvironmental factors, including hormones. We have investigated the effect of progesterone on the migration of HMC-1⁵⁶⁰ mast cells toward CXCL12, a chemokine that controls the migration of mast cells into tissues. HMC-1⁵⁶⁰ mast cells were incubated with 1 nM to 1 µM progesterone for 24 h. Controls were run without progesterone. Cell migration toward CXCL12 was monitored with an in vitro assay, and statistical analysis of repeated experiments revealed that progesterone significantly reduced cell migration without increasing the number of apoptotic cells (P = 0.0084, n = 7). Differences between progesterone-treated and untreated cells were significant at 1 µM (P < 0.01, n = 7). Cells incubated with 1 µM progesterone showed no rearrangment of actin filaments in response to CXCL12. Progesterone also reduced the calcium response to CXCL12 and Akt phosphorylation. Cells incubated with progesterone had one-half the control concentrations of CXCR4 (mRNA, total protein, and membrane-bound protein). Progesterone also inhibited the migration of HMC-1⁵⁶⁰ cells transfected with hPR-B-pSG5 plasmid, which contained 2.5 times as much PR-B as the control. These transfected cells responded differently (P < 0.05, n = 5) from untreated cells to 1 nM progesterone. We conclude that progesterone reduces mast cell migration toward CXCL12 and that CXCR4 may be a progesterone target in mast cells.

chemotaxis; sex steroid; immune system