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Comment
. 2016 Jul 28;128(4):467-8.
doi: 10.1182/blood-2016-06-719849.

Dampening neutrophil integrins

Rodger P McEver  1
Affiliations
Comment

Dampening neutrophil integrins

Rodger P McEver. Blood. .

Abstract

In this issue of Blood, Artz et al show that growth differentiation factor 15 (GDF-15), a distant relative of transforming growth factor β (TGF-β), inhibits neutrophil integrin activation through canonical TGF-β receptor heterodimers.

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Conflict of interest statement

Conflict-of-interest disclosure: The author holds equity in Selexys and Tetherex Pharmaceuticals.

Figures

None
Signals transmitted through chemokine receptors on rolling neutrophils activate the GTPase Rap-1, in part through CalDAG-GEFI. GTP-bound Rap-1 acts through effectors to convert integrin αLβ2 to an extended, high-affinity conformation, which mediates neutrophil arrest by binding ICAM-1 on endothelial cells. Artz et al demonstrate that TGF-β1 and the distantly related GDF-15 transmit signals through TGF-β–receptor heterodimers, which activate the GTPase Cdc42. GTP-bound Cdc42 inhibits activation of Rap-1, likely by interfering with CalDAG-GEFI. Cdc42, cell division protein 42; GDP, guanosine diphosphate. Illustration by Tadayuki Yago.
See this image and copyright information in PMC

Comment on

References

    1. Artz A, Butz S, Vestweber D. GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer. Blood. 2016;128(4):529–541. - PubMed
    1. Lefort CT, Ley K. Neutrophil arrest by LFA-1 activation. Front Immunol. 2012;3:157. - PMC - PubMed
    1. Calderwood DA, Campbell ID, Critchley DR. Talins and kindlins: partners in integrin-mediated adhesion. Nat Rev Mol Cell Biol. 2013;14(8):503–517. - PMC - PubMed
    1. Yago T, Petrich BG, Zhang N, et al. Blocking neutrophil integrin activation prevents ischemia-reperfusion injury. J Exp Med. 2015;212(8):1267–1281. - PMC - PubMed
    1. Bolomini-Vittori M, Montresor A, Giagulli C, et al. Regulation of conformer-specific activation of the integrin LFA-1 by a chemokine-triggered Rho signaling module. Nat Immunol. 2009;10(2):185–194. - PubMed