Expression and Role of Myeloid-related Protein-14 in Clinical and Experimental Sepsis

Zoelen, Marieke A. D. van; Vogl, Thomas; Foell, Dirk; Veen, Suzanne Q. van; Till, J. W. Olivier van; Florquin, Sandrine; Tanck, Michael W.T.; Wittebole, Xavier; Laterre, Pierre‐François; Boermeester, Marja A.; Roth, Johannes; Poll, Tom van der

doi:10.1164/rccm.200810-1552oc

Cited by 118 publications

(115 citation statements)

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“…Human pneumonia is associated with local and systemic MRP8/14 release [36,37], which correlates with findings in murine pneumonia caused by Klebsiella pneumoniae [20] or pneumococci [14,37]. In accordance, in the current model of S. aureus pneumonia, MRP8/14 levels in plasma and lungs were also increased.…”

Section: Discussionsupporting

confidence: 87%

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

et al. 2015

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Staphylococcus aureus has evolved as an important cause of pneumonia in both hospital and community settings. Staphylococcal lung infection can lead to overwhelming pulmonary inflammation. During infection, neutrophils release complexes of myeloid-related protein (MRP)8 and MRP14 (MRP8/ 14). MRP8/14 has been shown to exert pro-inflammatory and chemotactic activity, and to assist in the killing of S. aureus. In the current study we sought to determine the role of MRP8/14 in the host response during S. aureus pneumonia.Pneumonia was induced in wildtype and MRP14-deficient mice (mice unable to form MRP8/14) by intranasal inoculation of 1×10 7 CFU of S. aureus USA300. Mice were sacrificed at 6, 24, 48 or 72 h after infection for analyses.S. aureus pneumonia was associated with a strong rise in MRP8/14 in bronchoalveolar lavage fluid and lung tissue. Surprisingly, MRP14 deficiency had a limited effect on bacterial clearance and was associated with increased cytokine levels in bronchoalveolar lavage fluid and aggravated lung histopathology. MRP14 deficiency in addition was associated with a diminished transmigration of neutrophils into bronchoalveolar lavage fluid at late time-points after infection together with reduced release of nucleosomes.MRP8/14 serves in an unexpected protective role for the lung in staphylococcal pneumonia. @ERSpublications MRP8/14 unexpectedly protects against excessive pulmonary inflammation in murine staphylococcal pneumonia http://ow.ly/IwYt6

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Section: Discussionsupporting

confidence: 87%

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

et al. 2015

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“…The Mrp8/14 complex is known to be a ligand for TLR4 of which Mrp8 is the active component causing the increased expression of TNF-␣ . In patients with sepsis and in healthy humans injected with LPS, elevated Mrp8/14 plasma levels are observed [34] . Furthermore, it was shown that Mrp8/14 is released locally during severe infection in patients with peritonitis [34] .…”

Section: Myeloid-related Proteins Mrp8 and Mrp14mentioning

confidence: 99%

“…In patients with sepsis and in healthy humans injected with LPS, elevated Mrp8/14 plasma levels are observed [34] . Furthermore, it was shown that Mrp8/14 is released locally during severe infection in patients with peritonitis [34] . Investigations seeking to provide insight into the functional role of MRP8/14 revealed that Mrp14 contributes to bacterial dissemination and liver injury during abdominal sepsis [34] .…”

Section: Myeloid-related Proteins Mrp8 and Mrp14mentioning

confidence: 99%

“…Furthermore, it was shown that Mrp8/14 is released locally during severe infection in patients with peritonitis [34] . Investigations seeking to provide insight into the functional role of MRP8/14 revealed that Mrp14 contributes to bacterial dissemination and liver injury during abdominal sepsis [34] . In addition, mice lacking Mrp8-Mrp14 complexes are protected from endotoxin-induced lethal shock and E. coli induced abdominal sepsis [33] .…”

Section: Myeloid-related Proteins Mrp8 and Mrp14mentioning

confidence: 99%

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The Systemic Pro-Inflammatory Response in Sepsis

Jong

Poll²,

Wiersinga³

2010

J Innate Immun

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The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase proteins while the predominant cellular components are leukocytes and the endothelium. High-throughput genetic profiling studies have led to increased insights into leukocyte regulation during sepsis. New players in the pro-inflammatory cytokine network include interleukin-17, high-mobility group box-1 protein, macrophage migration inhibitory factor, the myeloid-related proteins Mrp8 and Mrp14, and soluble triggering receptor expressed on myeloid cells-1. Activation of coagulation with concurrent downregulation of anticoagulant systems and fibrinolysis are almost universally present in septic patients with SIRS. Increasing evidence points to an extensive cross-talk between inflammation and coagulation, in which the protease-activated cell receptors play an important role. Sepsis causes excessive activation of the complement system in which C5a plays a key part. Further dissection of the role of host-pathogen interactions, the cytokine network, the coagulation cascade, the complement system and their multidirectional interactions in sepsis will pave the way for new treatment targets that can modify the excessive and collective activation of all these systems.

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“…Thus, MRP-14 enhances innate host-defense mechanisms. Rather, MRP-14 mice appeared to be protected from endotoxemia [35], suggesting that excessive MRP-14 concentration might be harmful, an observation that had also been made for a sudden increase of other cytokines [36].…”

Section: Mrp-14 In the Peripheral Blood Of Patients With Infection Anmentioning

confidence: 94%

Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation

Dapunt

Giese

Maurer

et al. 2015

Journal of Leukocyte Biology

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Bone infections of patients with joint replacement by endoprosthesis (so called “periprosthetic joint infection”) pose a severe problem in the field of orthopedic surgery. The diagnosis is often difficult, and treatment is, in most cases, complicated and prolonged. Patients often require an implant exchange surgery, as the persistent infection and the accompanying inflammation lead to tissue damage with bone degradation and consequently, to a loosening of the implant. To gain insight into the local inflammatory process, expression of the proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to subsequent bone degradation was evaluated. We found MRP-14 prominently expressed in the affected tissue of patients with implant-associated infection, in close association with the chemokine CXCL8 and a dense infiltrate of neutrophils and macrophages. In addition, the number of MRP-14-positive cells correlated with the presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were significantly higher in patients with implant-associated infection compared with patients with sterile inflammation or healthy individuals, advocating MRP-14 as a novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP-14 directly induced the differentiation of monocytes to osteoclasts, thus linking the inflammatory response in implant infections with osteoclast generation, bone degradation, and implant loosening.

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Expression and Role of Myeloid-related Protein-14 in Clinical and Experimental Sepsis

Abstract: Human sepsis and endotoxemia are associated with enhanced release of MRP8/14. In abdominal sepsis, MRP8/14 likely occurs primarily at the site of the infection, facilitating bacterial dissemination at an early phase and liver injury.

Cited by 118 publications

References 56 publications

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

The Systemic Pro-Inflammatory Response in Sepsis

Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation

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