Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.
Monika PruensterAngela R M KurzKyoung-Jin ChungXiao Cao-EhlkerStephanie BieberClaudia F NussbaumSusanne BierschenkTanja K EggersmannIna RohwedderKristina HeinigRoland ImmlerMarkus MoserUwe KoedelSandra GranRodger P McEverDietmar VestweberAdmar VerschoorTomas LeandersonTriantafyllos ChavakisJohannes RothThomas VoglMarkus SperandioPublished in: Nature communications (2015)
Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid β2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo.
Keyphrases
- toll like receptor
- cell migration
- immune response
- inflammatory response
- bone marrow
- cell adhesion
- dendritic cells
- acute myeloid leukemia
- induced apoptosis
- transcription factor
- small molecule
- genome wide
- living cells
- cell cycle arrest
- cell death
- fluorescent probe
- nuclear factor
- endoplasmic reticulum stress
- cystic fibrosis
- staphylococcus aureus