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Rapid leukocyte migration by integrin-independent flowing and squeezing

2008; Nature Portfolio; Volume: 453; Issue: 7191 Linguagem: Inglês

10.1038/nature06887

1476-4687

Tim Lämmermann, B. Bader, Susan J. Monkley, Tim Worbs, Roland Wedlich‐Söldner, Karin Hirsch, Markus Keller, Reinhold Förster, David R. Critchley, Reinhard Fässler, Michael Sixt,

Cell Adhesion Molecules Research

All metazoan cells carry transmembrane receptors of the integrin family, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In agreement with this principle, rapidly migrating leukocytes use integrin-mediated adhesion when moving over two-dimensional surfaces. As migration on two-dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three-dimensional movement of leukocytes within tissues has remained controversial. We studied the interplay between adhesive, contractile and protrusive forces during interstitial leukocyte chemotaxis in vivo and in vitro. We ablated all integrin heterodimers from murine leukocytes, and show here that functional integrins do not contribute to migration in three-dimensional environments. Instead, these cells migrate by the sole force of actin-network expansion, which promotes protrusive flowing of the leading edge. Myosin II-dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus. Leukocytes are remarkable in their ability to infiltrate any type of tissue almost anywhere in the body. On flat surfaces they migrate using transmembrane receptors of the integrin family — present in all metazoan cells — that couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. But studies of cell migration on two-dimensional surfaces overemphasize the role of adhesion. The rapid movement and extreme flexibility of leukocytes in three dimensions is now shown — by genetic knockout — not to involve integrins. Instead, the cells migrate using an amoeba-like flowing and squeezing action, powered by actin network expansion alone. Leukocyte migration over two-dimensional surfaces is dependent on the integrin family of adhesion receptors, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In this study, all integrin heterodimers from mouse leukocytes were ablated and it is shown that integrins are not required for migration in 3D environments, in vitro and in vivo. Such non-adhesive migration renders leukocytes autonomous from the tissue environment.