Platelets support pulmonary recruitment of neutrophils in abdominal sepsis*

Asaduzzaman, Muhammad; Lavasani, Shahram; Rahman, Milladur; Zhang, Su; Braun, Öscar; Jeppsson, Bengt; Thorlacius, Henrik

doi:10.1097/ccm.0b013e31819ceb71

Cited by 134 publications

(132 citation statements)

References 48 publications

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“…However, results from that investigation are difficult to interpret because of inconsistencies in inflammatory responses and bacterial counts. For example, Meng et al (34) reported that pulmonary accumulation of neutrophils were lower 24 h compared with 6 h after CLP, which is in contrast to most studies on CLP-induced neutrophil recruitment (4,6,43). Moreover, in that study, it was reported that rhDNAse decreased bacterial counts in the blood but not in the peritoneal cavity, lung, or liver 24 h after CLP induction.…”

contrasting

confidence: 48%

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

Luo

Zhang

Wang

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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106

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Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with recombinant human (rh)DNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green, and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity, and lung. Blood, peritoneal fluid, and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury, as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in plasma, peritoneal cavity, and lung. Administration of rhDNAse not only eliminated NET formation in plasma, peritoneal cavity, and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6, and high-mobility group box 1 (HMGB1) in plasma, as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α, and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of proinflammatory compounds in abdominal sepsis. Thus we conclude that NETs exert a proinflammatory role in septic lung injury.

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contrasting

confidence: 48%

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

Luo

Zhang

Wang

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

106

101

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“…In models of lung inflammation induced by acid or abdominal sepsis, platelet depletion prevents both inflammation and vascular leakage, [37][38][39] pointing to a potential role of platelets in vascular permeability during lung inflammation. However, it remains unclear whether leakage occurring in lungs is mediated directly by a platelet-derived mediator or via the overall enhancement of inflammation by platelets.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, plateletneutrophil and platelet-endothelial cell interactions are suggested to participate to leakage of vasculature in lungs and brain. [37][38][39][50][51][52] In addition, the 13 different receptor subtypes for serotonin are capable of mediating distinct functions. 53 Thus, the cell combination present in the vasculature and a unique pattern of expression of the various serotonin receptors might conceivably result in prevention versus promotion of vascular permeability.…”

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confidence: 99%

Platelets can enhance vascular permeability

Cloutier

Paré

Farndale

et al. 2012

Blood

207

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AbstractPlatelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.

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“…Activated neutrophils release tissue destructive substances, such as reactive oxygen species and proteolytic enzymes, which, in turn, cause lung edema and impaired gaseous exchange (13,22). One study reported that platelets exert a key role in activating neutrophils in polymicrobial sepsis (2). This platelet-dependent activation of neutrophils appears to be mediated by CD40 ligand (CD40L) secreted from activated platelets (26).…”

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confidence: 99%