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Myeloid-related protein-14 contributes to protective immunity in gram-negative pneumonia derived sepsis
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
Vise andre og tillknytning
2012 (engelsk)Inngår i: PLoS Pathogens, ISSN 1553-7374, Vol. 8, nr 10, s. e1002987-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis. Myeloid related protein 8 (MRP8, S100A8) and MRP14 (S100A9) are the most abundant cytoplasmic proteins in neutrophils. They can form MRP8/14 heterodimers that are released upon cell stress stimuli. MRP8/14 reportedly exerts antimicrobial activity, but in acute fulminant sepsis models MRP8/14 has been found to contribute to organ damage and death. We here determined the role of MRP8/14 in K. pneumoniae sepsis originating from the lungs, using an established model characterized by gradual growth of bacteria with subsequent dissemination. Infection resulted in gradually increasing MRP8/14 levels in lungs and plasma. Mrp14 deficient (mrp14(-/-)) mice, unable to form MRP8/14 heterodimers, showed enhanced bacterial dissemination accompanied by increased organ damage and a reduced survival. Mrp14(-/-) macrophages were reduced in their capacity to phagocytose Klebsiella. In addition, recombinant MRP8/14 heterodimers, but not MRP8 or MRP14 alone, prevented growth of Klebsiella in vitro through chelation of divalent cations. Neutrophil extracellular traps (NETs) prepared from wildtype but not from mrp14(-/-) neutrophils inhibited Klebsiella growth; in accordance, the capacity of human NETs to kill Klebsiella was strongly impaired by an anti-MRP14 antibody or the addition of zinc. These results identify MRP8/14 as key player in protective innate immunity during Klebsiella pneumonia.

sted, utgiver, år, opplag, sider
San Fransisco: Public Library of Science , 2012. Vol. 8, nr 10, s. e1002987-
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URN: urn:nbn:se:umu:diva-62801DOI: 10.1371/journal.ppat.1002987ISI: 000310530300042PubMedID: 23133376OAI: oai:DiVA.org:umu-62801DiVA, id: diva2:581087
Tilgjengelig fra: 2012-12-28 Laget: 2012-12-18 Sist oppdatert: 2018-06-08bibliografisk kontrollert

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