The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/7/153/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 1, July 7, 1997 153-158

Brief Definitive Reports

Polarization of Chemokine Receptors to the Leading Edge during Lymphocyte Chemotaxis

Marta Nieto*, José M.R. Frade{ddagger}, David Sancho*, Mario Mellado{ddagger}, Carlos Martinez-A{ddagger}, and Francisco Sánchez-Madrid*

From the * Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, E-28006, Madrid, Spain; and {ddagger} Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain

Leukocyte migration in response to cell attractant gradients or chemotaxis is a key phenomenon both in cell movement and in the inflammatory response. Chemokines are quite likely to be the key molecules directing migration of leukocytes that involve cell polarization with generation of specialized cell compartments. The precise mechanism of leukocyte chemoattraction is not known, however. In this study, we demonstrate that the CC chemokine receptors CCR2 and CCR5, but not cytokine receptors such as interleukin (IL)-2R{alpha}, IL-2Rβ, tumor necrosis factor receptor 1, or transforming growth factor βR, are redistributed to a pole in T cells that are migrating in response to chemokines. Immunofluorescence and confocal microscopy studies show that the chemokine receptors concentrate at the leading edge of the cell on the flattened cell-substratum contact area, induced specifically by the signals that trigger cell polarization. The redistribution of chemokine receptors is blocked by pertussis toxin and is dependent on cell adhesion through integrin receptors, which mediate cell migration. Chemokine receptor expression on the leading edge of migrating polarized lymphocytes appears to act as a sensor mechanism for the directed migration of leukocytes through a chemoattractant gradient.

Address correspondence to Francisco Sánchez-Madrid Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Diego de León 62, E-28006, Madrid, Spain. Phone: 34-1-402-3347; FAX: 34-1-309-2496; E-mail: fsmadrid/princesa{at}hup.es


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