Magnetic wire active microrheology of human respiratory mucus

AbstractMucus is a viscoelastic gel secreted by the pulmonary epithelium in the tracheobronchial region of the lungs. The coordinated beating of cilia in contact with the gel layer moves mucus upwards towards pharynx, removing inhaled pathogens and particles from the airways. The efficacy of this clearance mechanism depends primarily on the rheological properties of mucus. Here we use a magnetic wire based microrheology technique to study the viscoelastic properties of human mucus collected from human bronchus tubes. The response of wires between 5 and 80 µm in length to a magnetic rotating field is monitored by optical time-lapse microscopy and analyzed using constitutive equation models of rheology, including Maxwell and Kelvin-Voigt. The static shear viscosity and elastic modulus can be inferred from low frequency (10−3 − 10 rad s−1) measurements, leading to the evaluation of the mucin network relaxation time. This relaxation time is found to be widely distributed, from one to several hundred seconds. Mucus is identified as a viscoelastic liquid with an elastic modulus of 2.5 ± 0.5 Pa and a static viscosity of 100 ± 40 Pa s. Our work shows that beyond the established spatial variations in rheological properties due to microcavities, mucus exhibits secondary inhomogeneities associated with the relaxation time of the mucin network that may be important for its flow properties.

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Pulmonary Epithelium, Immunology and Development of Asthma: Breathing Together

Case Medical Research ◽

10.31525/ct1-nct04063631 ◽

2019 ◽

Author(s):

Keyword(s):

Pulmonary Epithelium

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Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211003983 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110039

Author(s):

Carlos A. Cañas ◽

Felipe Cañas ◽

Mario Bautista-Vargas ◽

Fabio Bonilla-Abadía

Keyword(s):

Tissue Factor ◽

Proinflammatory Cytokines ◽

Antiphospholipid Antibodies ◽

Therapeutic Strategies ◽

Prothrombotic State ◽

Pulmonary Epithelium ◽

Angiotensin Converting Enzyme 2 ◽

Patients With Heart Failure ◽

Inflammatory Effect

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

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Nitric oxide decreases lung liquid production via guanosine 3′,5′-cyclic monophosphate

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.5.l923 ◽

2001 ◽

Vol 280 (5) ◽

pp. L923-L929 ◽

Cited By ~ 6

Author(s):

James J. Cummings ◽

Huamei Wang

Keyword(s):

Nitric Oxide ◽

Pulmonary Epithelium ◽

Fetal Sheep ◽

Cgmp Analog ◽

Pulmonary Arterial ◽

Series Of Experiments ◽

Lung Liquid ◽

Tracer Dilution ◽

Induced Changes

We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid production ( J v ) in chronically instrumented fetal sheep. Forty-five studies were done in which J v was measured by a tracer dilution technique. Left pulmonary arterial flow (Qlpa) was measured by a Doppler flow probe. There were two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by either the pulmonary vascular or intraluminal route; in the second, we used agents to inhibit or enhance endogenous cGMP activity. When infused directly into the pulmonary circulation, 8-bromo-cGMP significantly increased Qlpa but had no effect on J v. Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on Qlpa but significantly reduced J v. Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast significantly enhanced, the effect of instilled NO on J v. Thus the reduction in lung liquid caused by NO appears to be mediated by cGMP, perhaps through a direct effect on the pulmonary epithelium.

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