Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis

Zhichao Fan, Sara McArdle, Alex Marki, Zbigniew Mikulski, Edgar Gutierrez, Britta Engelhardt, Urban Deutsch, Mark Ginsberg, Alex Groisman and Klaus Ley ()
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Zhichao Fan: La Jolla Institute for Allergy and Immunology
Sara McArdle: La Jolla Institute for Allergy and Immunology
Alex Marki: La Jolla Institute for Allergy and Immunology
Zbigniew Mikulski: La Jolla Institute for Allergy and Immunology
Edgar Gutierrez: University of California San Diego
Britta Engelhardt: Theodor Kocher Institute, University of Bern
Urban Deutsch: Theodor Kocher Institute, University of Bern
Mark Ginsberg: University of California San Diego
Alex Groisman: University of California San Diego
Klaus Ley: La Jolla Institute for Allergy and Immunology

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Neutrophils are essential for innate immunity and inflammation and many neutrophil functions are β2 integrin-dependent. Integrins can extend (E+) and acquire a high-affinity conformation with an ‘open’ headpiece (H+). The canonical switchblade model of integrin activation proposes that the E+ conformation precedes H+, and the two are believed to be structurally linked. Here we show, using high-resolution quantitative dynamic footprinting (qDF) microscopy combined with a homogenous conformation-reporter binding assay in a microfluidic device, that a substantial fraction of β2 integrins on human neutrophils acquire an unexpected E−H+ conformation. E−H+ β2 integrins bind intercellular adhesion molecules (ICAMs) in cis, which inhibits leukocyte adhesion in vitro and in vivo. This endogenous anti-inflammatory mechanism inhibits neutrophil aggregation, accumulation and inflammation.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12658

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DOI: 10.1038/ncomms12658

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