2020
DOI: 10.1097/shk.0000000000001691
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Direct Airway Instillation of Neutrophils Overcomes Chemotactic Deficits Induced by Injury

Abstract: Background: Trauma induces neutrophil migration toward injury sites, both initiating wound healing and protecting against local bacterial infection. We have previously shown that mitochondrial formyl peptides (mtFPs) released by injured tissues act as chemoattractants by ligating neutrophil (PMN) formyl peptide receptor 1 (FPR1). But this process can also internalize multiple neutrophil chemoattractant receptors and thus might limit neutrophil migration to the lung in response to bacteria. Our objective was to… Show more

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Cited by 7 publications
(8 citation statements)
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“…Finally, we applied human PMN to our mouse model described in Figure 1 to determine whether human PMN can clear bacteria in the lungs without damaging lungs. CONand PMN-treated group showed significantly increased bacterial clearance in the lungs (Figure 5) [44]. We also observed mice for up to 28 days after the application of human PMN.…”
Section: Human Pmn Clears Bacteria In the Lungs Without Causing Adver...mentioning
confidence: 59%
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“…Finally, we applied human PMN to our mouse model described in Figure 1 to determine whether human PMN can clear bacteria in the lungs without damaging lungs. CONand PMN-treated group showed significantly increased bacterial clearance in the lungs (Figure 5) [44]. We also observed mice for up to 28 days after the application of human PMN.…”
Section: Human Pmn Clears Bacteria In the Lungs Without Causing Adver...mentioning
confidence: 59%
“…To mimic sterile, typical abdominal extrapulmonary injury in humans, we instilled mtDAMPs intraperitoneally (i.p.). This injury decreased the number of PMN migrating toward secondary infection in the lungs, thus bacterial clearance was reduced compared to control mice [7,14,44].…”
Section: Mouse Injury and Lung Infection Modelmentioning
confidence: 94%
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“…Detected by surface expressed formyl peptide receptor (FPR) 1 and FPR2 ( 67 ), mtFPs are neutrophil chemoattractants, with the proteins that most closely resemble bacterial-derived formylated peptides, namely ND3, ND4, ND5 and ND6 possessing the greatest chemotactic potency ( 66 ). Data generated by several studies have demonstrated that neutrophils pre-treated with ND6 exhibit reduced calcium fluxes, chemotactic responses and ROS production upon secondary stimulation with other GPCR agonists such as IL-8, leukotriene B4 (LTB 4 ) and fMLP ( 30 , 65 68 ). Contributing to this heterologous receptor desensitisation and suppression in anti-microbial functions is an ND6-mediated downregulation of GPCRs, for which activation of GRK2 is a potential underlying mechanistic explanation ( 63 , 65 , 66 , 218 ).…”
Section: Immunosuppressive Properties Of Dampsmentioning
confidence: 99%
“…Along this similar theme, Zhang et al (9) examined the role of mitochondrial formyl peptides (mtFPs) released by injured tissue in impaired neutrophil migration to the alveolar space. Using conditioned media generated by exposing peripheral blood mononuclear cells (PBMCs) to bacteria, the authors characterize essential PBMC-derived chemoattractants that are potent drivers of neutrophil chemotaxis.…”
mentioning
confidence: 99%