Am J Respir Crit Care Med
November 2022
MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
September 2022
The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how more than 90% of this barrier, made of AT1 (alveolar type 1) cells, responds to injury. Using the Sendai virus to model natural infection in mice, we find evidence that AT1 cells have an intermediary role by persisting in areas depleted of AT2 cells, upregulating IFN responsive genes, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2 (Sry-box 2) clusters without differentiating into AT1 or AT2 cells.
View Article and Find Full Text PDFMembrane fusion triggered by Ca is orchestrated by a conserved set of proteins to mediate synaptic neurotransmitter release, mucin secretion and other regulated exocytic processes. For neurotransmitter release, the Ca sensitivity is introduced by interactions between the Ca sensor synaptotagmin and the SNARE complex, and sequence conservation and functional studies suggest that this mechanism is also conserved for mucin secretion. Disruption of Ca-triggered membrane fusion by a pharmacological agent would have therapeutic value for mucus hypersecretion as it is the major cause of airway obstruction in the pathophysiology of respiratory viral infection, asthma, chronic obstructive pulmonary disease and cystic fibrosis.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
December 2020
Viral pneumonias remain global health threats, as exemplified in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, requiring novel treatment strategies both early and late in the disease process. We have reported that mice treated before or soon after infection with a combination of inhaled Toll-like receptor (TLR) 2/6 and 9 agonists (Pam2-ODN) are broadly protected against microbial pathogens including respiratory viruses, but the mechanisms remain incompletely understood. The objective of this study was to validate strategies for immune modulation in a preclinical model of viral pneumonia and determine their mechanisms.
View Article and Find Full Text PDFBackground And Purpose: Respiratory viral infections play central roles in the initiation, exacerbation and progression of asthma in humans. An acute paramyxoviral infection in mice can cause a chronic lung disease that resembles human asthma. We sought to determine whether reduction of Sendai virus lung burden in mice by stimulating innate immunity with aerosolized Toll-like receptor (TLR) agonists could attenuate the severity of chronic asthma-like lung disease.
View Article and Find Full Text PDFPlatelet degranulation is crucial for hemostasis and may participate in inflammation. Exocytosis in platelets is mediated by SNARE proteins and should be controlled by Munc13 proteins. We found that platelets express Munc13-2 and -4.
View Article and Find Full Text PDFAirway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion.
View Article and Find Full Text PDFObjective: Osteoporosis and periodontitis are common disorders that affect aging populations. It has been hypothesized that both conditions may be related. The aim of this study was to evaluate the relationship between osteoporosis and periodontitis using vertebral fragility fracture as a real marker of osteoporosis and periodontal clinical examination to define periodontitis.
View Article and Find Full Text PDFPurpose: To obtain analytical formulas for calculating the ocular rotation and the prismatic effect with a general lens, centered or decentered, with particular reference to thick spherotoric spectacle lenses.
Methods: Linear theory is used, using the symplectic properties of optical matrices, to derive the desired formulas.
Results: By applying the general formulas to particular cases, the corresponding formulas are obtained, sometimes recovering formulas already known.
Purpose: The purpose of this article is to compare different approximate formulas to compute the prismatic effect in axially symmetric spectacle lenses.
Methods: Gaussian formulas to calculate the prismatic effect are derived, for thick and thin lenses, and for near and far vision. The results from these formulas, as well as other taken from the literature, are compared with the exact results.