Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9

Blázquez-Prieto, Jorge; López-Alonso, Inés; Amado-Rodríguez, Laura; Huidobro, Covadonga; González-López, Adrián; Kuebler, Wolfgang M.; Albaiceta, Guillermo M.

doi:10.1136/thoraxjnl-2017-210105

Cited by 47 publications

(41 citation statements)

References 33 publications

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“…For example, in STRIVE, patients received a continuous effusion of 0.16 mg/kg/hour of Sivelestat after the onset of established ALI,6 in murine studies the doses used tended to be much higher (eg, 3 mg/kg/hour) and dosing regimens started much earlier after the initial insult 4. All these factors might contribute to the differing results seen in some human and animal models of ALI; however, it is the similarity of the human and murine results in the current study of ALI8 which is of interest and may provide insight into the changing roles of the neutrophil following lung injury.…”

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confidence: 71%

“…There is considerable uncertainty as to whether the neutrophil is a friend or foe in the development of this condition. The current paper by Blázquez-Prieto et al ,8 in a series of elegant experiments, provides mechanistic insight into this dilemma and suggests neutrophils might be both.…”

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confidence: 77%

“…It is clear from neutropenic adults that ALI can occur without a functional neutrophil response, therefore neutrophils may not be necessary for the initiation of lung injury. The current paper8 does not assess whether neutrophil depletion prior to VILI would still result in an inflammatory response and tissue injury consistent with ARDS using this model. Also, most adults with acquired neutropenia who go on to develop ALI also have deficits in other immune cells, which might alter clinical outcomes.…”

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confidence: 94%

“…The current paper8 builds on this finding by studying the effects of neutropenia when induced 24 hours following a VILI. Histological lung injury scores were significantly higher in the VILI and then neutrophil depleted mice at 48 hours’ recovery, as were the proinflammatory mediators tumour necrosis factor (TNF)α, interferon (IFN)γ and macrophage inflammatory protein-2, compared with the VILI and neutrophil replete group.…”

mentioning

confidence: 95%

“…For example, neutrophils have been described as senescent15 and immunosuppressive16 (thought to potentially contribute to the immunosuppression seen after sepsis17) although the physiological and pathological relevance of these phenotypes is as yet unclear. A neutrophil phenotype of potential relevance to the current study8 is the so-called ‘angiogenic neutrophil’; a subset which makes up 3% of neutrophils, identified by being CD49d + VEGFR1 high CXCR4 high and characterised by increased MMP-9 release 18…”

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confidence: 99%

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Friend or foe? The dual role of neutrophils in lung injury and repair

Grudzinska

Sapey

2018

Thorax

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confidence: 71%

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confidence: 77%

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confidence: 94%

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confidence: 95%

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confidence: 99%

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Friend or foe? The dual role of neutrophils in lung injury and repair

Grudzinska

Sapey

2018

Thorax

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Systemic Transplantation of Eyelid Adipose‐Derived Stem Cells for Antifibrotic Treatment

Fang

Chen

Teng

et al. 2020

Advanced Therapeutics

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Fibrosis is a result of the pathological wound‐healing response initiated by immune cells and leads to permanent scarring, such as corneal scarring, which impairs the vision of millions of people worldwide. However, there is currently no available treatment strategy that specifically targets the pathogenesis of fibrosis and can be translated in a safe and versatile way. Herein, it is illustrated that systemic transplantation of easily accessible human eyelid adipose‐derived stem cells (heADSCs) can successfully and safely exert antifibrotic effects in both corneal and skin scarring cases. Intravenous injection of heADSCs alleviates scar formation after rat corneal lamellar injury with accelerated epithelization, increases tumor necrosis factor‐stimulated gene‐6 (TSG‐6) in the epithelium, and decreases inflammatory factors. Cell tracing shows the presence of detectable signals until the 7th day, while no pulmonary embolism or other discomfort occurs. heADSCs effectively reduce corneal scarring by ameliorating stromal inflammation by increasing endogenous tissue‐protective TSG‐6 in the epithelium and macrophage phenotype switching, which is more effective with systemic transplantation than subconjunctival transplantation. Systemic transplantation of heADSCs shows safe antifibrotic effects in both corneal and skin scarring cases and this result identifies systemic transplantation with autologous adipose‐derived stem cells as a generally versatile and safe therapy for antifibrotic treatment.

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ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

Stephens

2020

Evidence-Based Critical Care

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A 44 year-old woman with a history of acute myeloid leukemia (AML) underwent a non-myeloablative haploidentical peripheral blood hematopoietic stem cell transplant (HSCT) 10 days ago. She was admitted to the hospital with fevers to 39 °C. On examination, she is anxious-appearing, with a temperature of 38.9 °C, a heart rate of 120 beats/min, a respiratory rate of 28 breaths/min, a blood pressure of 98/64 mmHg, and an oxygen saturation of 94% on 4 L/min oxygen via nasal cannula. A tunneled central venous catheter is in situ in her right internal jugular vein. Her total white blood cell (WBC) count is <0.5 cells/mm 3 and platelet count is 8000 cells/mm 3 . A chest CT scan shows diffuse patchy bilateral infiltrates (Figure). She is started on empiric antibiotic coverage with piperacillin/tazobactam, and 3 L of crystalloid are administered. Several hours later, she is more hypotensive, with nadir systolic pressures of 80-88 mmHg, and is more hypoxic, now saturating 85% on 6 L/min nasal cannula oxygen. QuestionHow should this patient be managed?Answer Broad spectrum antibiotics and lung-protective respiratory support.All patients after HSCT are immunosuppressed, profoundly so in the early post-transplant period before engraftment has occurred. This patient is likely to have a pneumonia with secondary septic shock, but a central line-associated infection from her tunneled central line is possible, as are non-infectious complications of HSCT. Respiratory failure is the most frequent cause of intensive care unit (ICU) admission after HSCT, most frequently from an infectious cause. The patient was placed on high-flow nasal cannula (HFNC) for oxygenation support and started on a norepinephrine infusion for hemodynamic support. Antibacterial coverage was changed to meropenem, levofloxacin, and vancomycin, and voriconazole was added for antifungal coverage. Her central line was removed. Her respiratory status continued to decline, and endotracheal intubation and mechanical ventilation were required 24 h after admission. She was placed on volume assist-control with a tidal volume of 6 mL/kg predicted body weight, and bronchoscopy with bronchoalveolar lavage (BAL) was performed. The BAL fluid was initially bloody, but cleared with sequential aliquots. Microbiologic studies of the BAL fluid were positive for respiratory syncytial virus and Pseudomonas aeruginosa. She was maintained on low tidal-volume ventilation and vasopressors were weaned off. Her white blood cell count slowly began to recover, and her respiratory status began to improve. She was extubated on hospital day 12 and was discharged from the ICU on hospital day 14. Principles of ManagementHematopoietic stem cell transplant (HSCT) has become an essential therapeutic modality in the treatment of malignant and non-malignant hematologic disease. In 2016, more than 23,000 HSCTs were performed in the United States, including approximately 15,000 autologous HSCTs and more than 8500 allogeneic transplants [1]. Allogeneic transplants are associated with more morbidity and m...

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Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9

Abstract: Release of MMP-9 from neutrophils is required for adequate matrix processing and lung repair.

Cited by 47 publications

References 33 publications

Friend or foe? The dual role of neutrophils in lung injury and repair

Friend or foe? The dual role of neutrophils in lung injury and repair

Systemic Transplantation of Eyelid Adipose‐Derived Stem Cells for Antifibrotic Treatment

ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

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