Effects of airway smooth muscle contraction and inflammation on lung tissue compliance

Boucher, Magali; Henry, Cyndi; Khadangi, Fatemeh; Dufour-Mailhot, Alexis; Tremblay-Pitre, Sophie; Fereydoonzad, Liah; Brunet, David; Robichaud, Annette; Bossé, Ynuk

doi:10.1152/ajplung.00384.2021

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…6J-K ) and quantified differences as measured by hysteresis ( Fig. 6L ) ( 68, 69 ). Prior to methacholine challenge, prenatal inflammation alone significantly impaired respiratory function regardless of saline or papain challenge, whereas papain alone had no significant effect on respiratory function in saline-exposed offspring, consistent with worsened histopathology in response to prenatal inflammation alone ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

López,

Griffin,

Aguilar

et al. 2023

Preprint

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Allergic asthma is a chronic respiratory disease that initiates in early life, but causal mechanisms are poorly understood. Here we examined how prenatal inflammation shapes allergic asthma susceptibility by reprogramming lung immunity from early development. Induction of Type I interferon-mediated inflammation during development provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produced increased IL-5 and IL-13, and were associated with acute Th2 bias, eosinophilia, and decreased Tregs in the lung. The hyperactive ILC2 phenotype was recapitulated by adoptive transfer of a fetal liver precursor following exposure to prenatal inflammation, indicative of developmental programming. Programming of ILC2 function and subsequent lung immune remodeling by prenatal inflammation led to airway dysfunction at baseline and in response to papain, indicating increased asthma susceptibility. Our data provide a link by which developmental programming of progenitors by early-life inflammation drives lung immune remodeling and asthma susceptibility through hyperactivation of lung-resident ILC2s.One Sentence SummaryPrenatal inflammation programs asthma susceptibility by inducing the production of hyperactivated ILC2s in the developing lung.

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Section: Resultsmentioning

confidence: 99%

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

López,

Griffin,

Aguilar

et al. 2023

Preprint

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“…The two additional in vivo readouts include K and V 10 _TLC. They are both purportedly insensitive to lung volume 20 , 21 , and thus exclusively sensitive to lung tissue stiffness. They are currently considered volume-independent indicators of the compliance of the respiratory system 20 , 21 .…”

Section: Discussionmentioning

confidence: 99%

“…They are both purportedly insensitive to lung volume 20 , 21 , and thus exclusively sensitive to lung tissue stiffness. They are currently considered volume-independent indicators of the compliance of the respiratory system 20 , 21 . They were both significantly lower in C57BL/6 than BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

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Lung stiffness of C57BL/6 versus BALB/c mice

Rojas-Ruiz,

Boucher,

Gill

et al. 2023

Sci Rep

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This study was undertaken to determine whether a smaller lung volume or a stiffer lung tissue accounts for the greater lung elastance of C57BL/6 than BALB/c mice. The mechanical properties of the respiratory system and lung volumes were measured with the flexiVent and compared between male C57BL/6 and BALB/c mice (n = 9). The size of the excised lung was also measured by volume liquid displacement. One lobe was then subjected to sinusoidal strains in vitro to directly assess the mechanical properties of the lung tissue, and another one was used to quantify the content of hydroxyproline. In vivo elastance was markedly greater in C57BL/6 than BALB/c mice based on 5 different readouts. For example, respiratory system elastance was 24.5 ± 1.7 vs. 21.5 ± 2.4 cmH2O/mL in C57BL/6 and BALB/c mice, respectively (p = 0.007). This was not due to a different lung volume measured by displaced liquid volume. On the isolated lobes, both elastance and the hydroxyproline content were significantly greater in C57BL/6 than BALB/c mice. These results suggest that the lung elastance of C57BL/6 mice is greater than BALB/c mice not because of a smaller lung volume but because of a stiffer lung tissue due to a greater content of collagen.

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“…The deflating limb was analyzed using the Salazar-Knowles’s equation: V = A–B e −KP , where V is volume, A is the asymptote on the volume-axis (it is a fair estimate of IC but assessed in quasi-static conditions), B is the difference between A and the extrapolated volume at which pressure would cross zero, K is an exponent describing the curvature of the upper portion of the deflation limb of the P-V loop, and P is pressure. The parameter K is especially useful, since it is a volume-independent indicator of lung tissue compliance ( Boucher et al, 2022 ). Two additional parameters were calculated from the quasi-static P-V loop, namely quasi-static elastance (Est) and hysteresis (i.e., the area within the P-V loop).…”

Section: Methodsmentioning

confidence: 99%

Malat1 deficiency prevents hypoxia-induced lung dysfunction by protecting the access to alveoli

et al. 2022

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Hypoxia is common in lung diseases and a potent stimulator of the long non-coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1). Herein, we investigated the impact of Malat1 on hypoxia-induced lung dysfunction in mice. Malat1-deficient mice and their wild-type littermates were tested after 8 days of normoxia or hypoxia (10% oxygen). Hypoxia decreased elastance of the lung by increasing lung volume and caused in vivo hyperresponsiveness to methacholine without altering the contraction of airway smooth muscle. Malat1 deficiency also modestly decreased lung elastance but only when tested at low lung volumes and without altering lung volume and airway smooth muscle contraction. The in vivo responsiveness to methacholine was also attenuated by Malat1 deficiency, at least when elastance, a readout sensitive to small airway closure, was used to assess the response. More impressively, in vivo hyperresponsiveness to methacholine caused by hypoxia was virtually absent in Malat1-deficient mice, especially when hysteresivity, a readout sensitive to small airway narrowing heterogeneity, was used to assess the response. Malat1 deficiency also increased the coefficient of oxygen extraction and decreased ventilation in conscious mice, suggesting improvements in gas exchange and in clinical signs of respiratory distress during natural breathing. Combined with a lower elastance at low lung volumes at baseline, as well as a decreased propensity for small airway closure and narrowing heterogeneity during a methacholine challenge, these findings represent compelling evidence suggesting that the lack of Malat1 protects the access to alveoli for air entering the lung.

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Effects of airway smooth muscle contraction and inflammation on lung tissue compliance

Cited by 13 publications

References 31 publications

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

Lung stiffness of C57BL/6 versus BALB/c mice

Malat1 deficiency prevents hypoxia-induced lung dysfunction by protecting the access to alveoli

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