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* Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006-Madrid, Spain; The recruitment of leukocytes from the
bloodstream is a key step in the inflammatory reaction,
and chemokines are among the main regulators of this
process. During lymphocyte-endothelial interaction,
chemokines induce the polarization of T lymphocytes, with the formation of a cytoplasmic projection (uropod) and redistribution of several adhesion molecules
(ICAM-1,-3, CD43, CD44) to this structure. Although
it has been reported that these cytokines regulate the
adhesive state of integrins in leukocytes, their precise
mechanisms of chemoattraction remain to be elucidated. We have herein studied the functional role of the
lymphocyte uropod. Confocal microscopy studies
clearly showed that cell uropods project away from the
cell bodies of adhered lymphocytes and that polarized T cells contact other T cells through the uropod structure. Time-lapse videomicroscopy studies revealed that
uropod-bearing T cells were able, through this cellular
projection, to contact, capture, and transport additional
bystander T cells. Quantitative analysis revealed that
the induction of uropods results in a 5-10-fold increase
in cell recruitment. Uropod-mediated cell recruitment seems to have physiological relevance, since it was
promoted by both CD45R0+ peripheral blood memory
T cells as well as by in vivo activated lymphocytes. Additional studies showed that the cell recruitment mediated by uropods was abrogated with antibodies to
ICAM-1, -3, and LFA-1, whereas mAb to CD43, CD44,
CD45, and L-selectin did not have a significant effect,
thus indicating that the interaction of LFA-1 with
ICAM-1 and -3 appears to be responsible for this process. To determine whether the increment in cell
recruitment mediated by uropod may affect the
transendothelial migration of T cells, we carried out
chemotaxis assays through confluent monolayers of endothelial cells specialized in lymphocyte extravasation. An enhancement of T cell migration was observed under conditions of uropod formation, and this increase
was prevented by incubation with either blocking anti-
ICAM-3 mAbs or drugs that impair uropod formation.
These data indicate that the cell interactions mediated by cell uropods represent a cooperative mechanism in
lymphocyte recruitment, which may act as an amplification system in the inflammatory response.
Departamento de
Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, 28040-Madrid, Spain; § National
Institute for Medical Research, Division of Cellular Immunology, Medical Research Council, London NW7 1AA, United
Kingdom; Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, 28007-Madrid, Spain
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