Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

McGovern, Toby K.; Robichaud, Annette; Fereydoonzad, Liah; Schuessler, Thomas F.; Martin, James G.

doi:10.3791/50172

Cited by 102 publications

(115 citation statements)

References 27 publications

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“…Thus, although proinflammatory processes are elevated by C5a after LPS exposure in C5L2 2/2 mice, these processes, in turn, result in elevated production of suppressive processes. To determine whether the changes in inflammatory parameters observed after LPS administration to C5L2 2/2 and wildtype mice correlated with changes in lung physiology, we examined a number of mechanical parameters of the animals using a technique of forced oscillation to determine pressure and volume signals (31). Consistent with literature reports indicating little or no alteration in lung physiology despite increased inflammatory cell infiltrates and cytokine production (32, 33), our findings indicated that wild-type mice at 48 hours after LPS administration exhibited no significant change in total lung volume, resistance, or elastic recoil, although dynamic compliance was reduced ( Figures 6A-6D).…”

Section: C5l2mentioning

confidence: 99%

C5L2, the Second C5a Anaphylatoxin Receptor, Suppresses LPS-Induced Acute Lung Injury

Wang

Liu

Gérard

et al. 2016

Am J Respir Cell Mol Biol

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LPS-induced lung injury in the mouse is one of the most robust experimental models used for studies of acute lung injury (ALI) and acute respiratory distress syndrome in humans. Prior clinical and experimental studies support an important role for complement activation, particularly production of C5a, in the pathophysiology of human ALI/acute respiratory distress syndrome. In the mouse model, however, the precise role of C5a and its receptors is unclear. C5L2, an enigmatic second receptor for C5a, has been characterized, and results have generated substantial debate regarding its in vivo function. Our previous work with human neutrophils revealed a unique role for C5L2 in negatively modulating C5a-C5a receptor (C5aR)-mediated cellular activation, in which antibody-mediated blockade of C5L2 resulted in augmented C5a-C5aR responses. Here, we demonstrate that C5L2 2/2 mice (BALB/c background) administered intranasal LPS exhibit significantly more airway edema and hemorrhage than do wild-type animals. Bronchoalveolar lavage fluid and lung homogenates have significantly more neutrophils and myeloperoxidase activity, as well as proinflammatory cytokines and chemokines. When a blocking antibody against the C5aR was administered before LPS administration, the increased neutrophilic infiltration and cytokine levels were reversed. Thus, our data show not only that C5a contributes significantly to LPS-induced ALI in the mouse, but also that C5L2 plays an important antiinflammatory role in this model through actions resulting at least in part from negative modulation of C5a receptor activation.

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Section: C5l2mentioning

confidence: 99%

C5L2, the Second C5a Anaphylatoxin Receptor, Suppresses LPS-Induced Acute Lung Injury

Wang

Liu

Gérard

et al. 2016

Am J Respir Cell Mol Biol

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“…The mechanical properties of the respiratory system were assessed using single frequency (2.5 Hz; Snapshot-150, 1.2 s) and broadband forced oscillation signals (1-20.5 Hz; Quick Prime-3, 3 s) as well as a quasi-static, step-wise, pressure-controlled pressure-volume loop (PVs-P, 16 s) (McGovern et al, 2013). The linear single-compartment model was used to evaluate total respiratory resistance (R rs ) and elastance (E rs ) while the constant phase model allowed the partitioning of the responses within the lungs (Hantos et al, 1992).…”

Section: Methodsmentioning

confidence: 99%

Mechanical consequences of allergic induced remodeling on mice airway resistance and compressibility

Novali

Shalaby

Robichaud³

et al. 2015

Respiratory Physiology & Neurobiology

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“…This protocol uses a small animal ventilator to measure reductions in the elastic recoil of the lung (increases in quasistatic lung compliance [Cst] and reductions in tissue elastance [H]), PV flow loops, and changes in airway and tissue resistance in anesthetized mice (15,16) .…”

Section: Pulmonary Function Test (Pfts)mentioning

confidence: 99%

Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice

Laucho-Contreras

Taylor

Mahadeva

et al. 2015

JoVE

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COPD is projected to be the third most common cause of mortality world-wide by 2020 (1) . Animal models of COPD are used to identify molecules that contribute to the disease process and to test the efficacy of novel therapies for COPD. Researchers use a number of models of COPD employing different species including rodents, guinea-pigs, rabbits, and dogs (2) . However, the most widely-used model is that in which mice are exposed to cigarette smoke. Mice are an especially useful species in which to model COPD because their genome can readily be manipulated to generate animals that are either deficient in, or over-express individual proteins. Studies of gene-targeted mice that have been exposed to cigarette smoke have provided valuable information about the contributions of individual molecules to different lung pathologies in COPD (3)(4)(5) . Most studies have focused on pathways involved in emphysema development which contributes to the airflow obstruction that is characteristic of COPD. However, small airway fibrosis also contributes significantly to airflow obstruction in human COPD patients (6) , but much less is known about the pathogenesis of this lesion in smoke-exposed animals. To address this knowledge gap, this protocol quantifies both emphysema development and small airway fibrosis in smoke-exposed mice. This protocol exposes mice to CS using a whole-body exposure technique, then measures respiratory mechanics in the mice, inflates the lungs of mice to a standard pressure, and fixes the lungs in formalin. The researcher then stains the lung sections with either Gill's stain to measure the mean alveolar chord length (as a readout of emphysema severity) or Masson's trichrome stain to measure deposition of extracellular matrix (ECM) proteins around small airways (as a readout of small airway fibrosis). Studies of the effects of molecular pathways on both of these lung pathologies will lead to a better understanding of the pathogenesis of COPD. Video LinkThe video component of this article can be found at

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Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

Cited by 102 publications

References 27 publications

C5L2, the Second C5a Anaphylatoxin Receptor, Suppresses LPS-Induced Acute Lung Injury

C5L2, the Second C5a Anaphylatoxin Receptor, Suppresses LPS-Induced Acute Lung Injury

Mechanical consequences of allergic induced remodeling on mice airway resistance and compressibility

Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice

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