Fan, ZhichaoZhichaoFanMcArdle, SaraSaraMcArdleMarki, AlexAlexMarkiMikulski, ZbigniewZbigniewMikulskiGutierrez, EdgarEdgarGutierrezEngelhardt, BrittaBrittaEngelhardt0000-0003-3059-9846Deutsch, UrbanUrbanDeutschGinsberg, MarkMarkGinsbergGroisman, AlexAlexGroismanLey, KlausKlausLey2024-10-252024-10-252016-08-31https://boris-portal.unibe.ch/handle/20.500.12422/149743Neutrophils 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.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.953492757804910.1038/ncomms12658