| First Author | Fan Z | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12658 | PubMed ID | 27578049 |
| Mgi Jnum | J:241903 | Mgi Id | MGI:5903835 |
| Doi | 10.1038/ncomms12658 | Citation | Fan Z, et al. (2016) Neutrophil recruitment limited by high-affinity bent beta2 integrin binding ligand in cis. Nat Commun 7:12658 |
| abstractText | Neutrophils are essential for innate immunity and inflammation and many neutrophil functions are beta2 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 beta2 integrins on human neutrophils acquire an unexpected E(-)H(+) conformation. E(-)H(+) beta2 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. |
