A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice

Almeida, Aline Dias de; Silva, Irismara Sousa; Fernandes‐Braga, Weslley; LimaFilho, Antônio Carlos Melo; Florentino, Rodrigo M.; Barra, Alexandre de Almeida; Andrade, Luciana de Oliveira; Leite, M. Fátima; Cassali, Geovanni Dantas; Klein, André

doi:10.1007/s00011-020-01376-4

Cited by 20 publications

(15 citation statements)

References 58 publications

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“…Mice received 0.2 ml cromolyn or compound 48/80 intravenously at 5 min before the induction of SAH, while ENMD-1068 was administrated intravenously at 1 h before modeling. The deliver route and concentration of agents were obtained as previously reported ( Strbian et al, 2007 ; de Almeida et al, 2020 ). Animals in the sham-operated group and SAH + vehicle group received the same volume of saline.…”

Section: Methodsmentioning

confidence: 99%

Mast Cells Mediate Inflammatory Injury and Aggravate Neurological Impairment in Experimental Subarachnoid Hemorrhage Through Microglial PAR-2 Pathway

Qin

Peng

Chen

et al. 2021

Front. Cell. Neurosci.

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Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with high mortality and disability. Aberrant neuroinflammation has been identified as a critical factor accounting for the poor prognosis of SAH patients. Mast cells (MCs), the sentinel cells of the immune system, play a critical in the early immune reactions and participate in multiple pathophysiological process. However, the exact role of MCs on the pathophysiological process after SAH has not been fully understood. The current study was conducted to determine the role of MCs and MC stabilization in the context of SAH. Mouse SAH model was established by endovascular perforation process. Mice received saline or cromolyn (MC stabilizer) or compound 48/80 (MCs degranulator). Post-SAH evaluation included neurobehavioral test, western blot, immunofluorescence, and toluidine blue staining. We demonstrated that SAH induced MCs activation/degranulation. Administration of MC stabilizer cromolyn conferred a better neurologic outcome and decreased brain edema when compared with SAH+vehicle group. Furthermore, cromolyn significantly inhibited neuroinflammatory response and alleviated neuronal damage after SAH. However, pharmacological activation of MCs with compound 48/80 dramatically aggravated SAH-induced brain injury and exacerbated neurologic outcomes. Notably, pharmacological inhibition of microglial PAR-2 significantly reversed MCs-induced inflammatory response and neurological impairment. Additionally, the effect of MCs-derived tryptase in mediating neuroinflammation was also abolished by the microglial PAR-2 blockage in vitro. Taken together, MCs yielded inflammatory injury through activating microglia-related neuroinflammation after SAH. These data shed light on the notion that MCs might be a novel and promising therapeutic target for SAH.

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Section: Methodsmentioning

confidence: 99%

Mast Cells Mediate Inflammatory Injury and Aggravate Neurological Impairment in Experimental Subarachnoid Hemorrhage Through Microglial PAR-2 Pathway

Qin

Peng

Chen

et al. 2021

Front. Cell. Neurosci.

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“…Some studies revealed that tryptase-PAR2 may affect neurogenic inflammation and pain transmission via regulating the activity of TRP ankyrin 1 and TRPV1, TRPV4 channels of sensory neurons (Dai et al, 2004 , 2007 ; Zhao et al, 2014 ), by phospholipase C, protein kinase A, and protein kinase C-dependent mechanisms (Chen et al, 2011 ). Moreover, MC tryptase activates neutrophil (de Almeida et al, 2020 ) and microglia (Zhang S. et al, 2012 ), which are important culprits for inflammation and exerts an active role in pain (Tsuda, 2018 ). MC tryptase has been implicated in peripheral and central sensitization, albeit there remain large gaps in our knowledge about the tryptase-mediated mechanism of nociception.…”

Section: Mechanistic Insights Into the Dialog Between Neuron And Mast Cellmentioning

confidence: 99%

Involvement of Mast Cells in the Pathophysiology of Pain

Mai

Liu

Huang

et al. 2021

Front. Cell. Neurosci.

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Mast cells (MCs) are immune cells and are widely distributed throughout the body. MCs are not only classically viewed as effector cells of some allergic diseases but also participate in host defense, innate and acquired immunity, homeostatic responses, and immunoregulation. Mounting evidence indicates that activation of MCs releasing numerous vasoactive and inflammatory mediators has effects on the nervous system and has been involved in different pain conditions. Here, we review the latest advances made about the implication of MCs in pain. Possible cellular and molecular mechanisms regarding the crosstalk between MC and the nervous system in the initiation and maintenance of pain are also discussed.

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“…Further, it has been suggested that the ability of MCs to recruit neutrophils is dependent on their release of neutrophil-attracting CXCL1/CXCL2 chemokines [ 12 ], whereas another study linked the neutrophil-attracting capacity of MCs to their expression of IL-33 [ 13 ]. It has also been shown that MCs can enhance neutrophil recruitment in the context of allograft rejection [ 14 ] and in several other settings [ 15 , 16 , 17 , 18 , 19 , 20 ]. However, adding complexity to this issue, it has been shown that MCs can have a dampening impact on neutrophil recruitment in a setting of acute ischemic kidney injury [ 21 ], and MC products have been shown to be cytotoxic for neutrophils [ 22 ] and to limit neutrophil recruitment by degrading TNF [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Mast Cell Tryptase Potentiates Neutrophil Extracellular Trap Formation

et al. 2021

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Previous research has indicated an intimate functional communication between mast cells (MCs) and neutrophils during inflammatory conditions, but the nature of such communication is not fully understood. Activated neutrophils are known to release DNA-containing extracellular traps (neutrophil extracellular traps [NETs]) and, based on the known ability of tryptase to interact with negatively charged polymers, we here hypothesized that tryptase might interact with NET-contained DNA and thereby regulate NET formation. In support of this, we showed that tryptase markedly enhances NET formation in phorbol myristate acetate-activated human neutrophils. Moreover, tryptase was found to bind vividly to the NETs, to cause proteolysis of core histones and to cause a reduction in the levels of citrullinated histone-3. Secretome analysis revealed that tryptase caused increased release of numerous neutrophil granule compounds, including gelatinase, lactoferrin, and myeloperoxidase. We also show that DNA can induce the tetrameric, active organization of tryptase, suggesting that NET-contained DNA can maintain tryptase activity in the extracellular milieu. In line with such a scenario, DNA-stabilized tryptase was shown to efficiently degrade numerous pro-inflammatory compounds. Finally, we showed that tryptase is associated with NET formation in vivo in a melanoma setting and that NET formation in vivo is attenuated in mice lacking tryptase expression. Altogether, these findings reveal that NET formation can be regulated by MC tryptase, thus introducing a novel mechanism of communication between MCs and neutrophils.

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A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice

Cited by 20 publications

References 58 publications

Mast Cells Mediate Inflammatory Injury and Aggravate Neurological Impairment in Experimental Subarachnoid Hemorrhage Through Microglial PAR-2 Pathway

Mast Cells Mediate Inflammatory Injury and Aggravate Neurological Impairment in Experimental Subarachnoid Hemorrhage Through Microglial PAR-2 Pathway

Involvement of Mast Cells in the Pathophysiology of Pain

Mast Cell Tryptase Potentiates Neutrophil Extracellular Trap Formation

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