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Diabetes 53:1285-1292, 2004
© 2004 by the American Diabetes Association, Inc.

From Blood Monocytes to Adipose Tissue-Resident Macrophages

Induction of Diapedesis by Human Mature Adipocytes

Cyrile A. Curat1, Alexandra Miranville1, Coralie Sengenès1, Michael Diehl2, Carolin Tonus3, Rudi Busse1, and Anne Bouloumié1,4

1 Department of Cardiovascular Physiology, J.W. Goethe University, Frankfurt am Main, Germany
2 Department of Internal Medicine II, Klinikum Offenbach, Offenbach, Germany
3 Department of Surgery I, Klinikum Offenbach, Offenbach, Germany
4 Obesity Research Unit, INSERM U 586, Université Paul Sabatier, Toulouse, France

Obesity has been suggested to be a low-grade systemic inflammatory state, therefore we studied the interaction between human adipocytes and monocytes via adipose tissue (AT)-derived capillary endothelium. Cells composing the stroma-vascular fraction (SVF) of human ATs were characterized by fluorescence-activated cell sorter (FACS) analysis and two cell subsets (resident macrophages and endothelial cells [ECs]) were isolated using antibody-coupled microbeads. Media conditioned by mature adipocytes maintained in fibrin gels were applied to AT-derived ECs. Thereafter, the expression of endothelial adhesion molecules was analyzed as well as the adhesion and transmigration of human monocytes. FACS analysis showed that 11% of the SVF is composed of CD14+/CD31+ cells, characterized as resident macrophages. A positive correlation was found between the BMI and the percentage of resident macrophages, suggesting that fat tissue growth is associated with a recruitment of blood monocytes. Incubation of AT-derived ECs with adipocyte-conditioned medium resulted in the upregulation of EC adhesion molecules and the increased chemotaxis of blood monocytes, an effect mimicked by recombinant human leptin. These results indicate that adipokines, such as leptin, activate ECs, leading to an enhanced diapedesis of blood monocytes, and suggesting that fat mass growth might be linked to inflammatory processes.


Address correspondence and reprint requests to Cyrile A. Curat, Institut für Kardiovaskuläre Physiologie, J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60 596 Frankfurt/Main, Germany. E-mail: curat{at}zphys1.uni-frankfurt.de


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Copyright © 2004 by the American Diabetes Association.