Proteins respiratory mucus

Barriers to pulmonary absorption of proteins and peptides include respiratory mucus, mucociliary clearance, pulmonary enzymes/proteases, alveolar lining layer, alveolar epithelium, basement membrane, macrophages and other cells [3, 18]. The molecular weight cutoff of tight junctions for alveolar type I cells is 0.6 nm, while endothelial junctions allow the passage of larger molecules (4-6 nm). In order to reach the bloodstream in the endothelial vasculature, proteins and peptides must cross this alveolar epithelium, the capillary endothelium, and the intervening extracellular matrix. 

Respiratory mucus is a complex mixture of glycoproteins, proteoglycans, lipids, and smaller quantities of other proteins (82). Glycoproteins appear to be the most important component conferring viscoelastic properties to the mucus (see also Chap. 13). 

The third condition, late respiratory systemic syndrome, is characterized by cough, mucus production, occasional wheezing, and systemic symptoms of malaise, chills, fever, and aching muscles and joints, occurring 4—12 hours alter exposure. This syndrome also has been termed TMA flu and clinically resembles hypersensitivity pneumonitis with visible chest X-ray infiltrates. High levels of IgG serum antibody and total serum antibody directed against trimellityl-human protein conjugates accompany the syndrome, and a latent period of exposure before the onset of symptoms is typical. 

Aerosolized DNase (dornase) is a therapeutic protein designed for alveoli delivery to achieve local effects in the deep lung. Aerosolized DNase is formulated as a pulmonary dosage form, targeted for deep-lung delivery to reduce opportunistic infections due to the increased viscosity of mucus in the lung that affects respiratory function in patients with cystic fibrosis. 

There is evidence that both occupational and environmental exposures to chemicals (both proteins and haptens) can result in the induction or exacerbation of respiratory allergies (Table 19.6). Of particular concern is the induction of allergic asthma. In sensitized asthmatic individuals the antigen challenge generally causes a type I (IgE-mediated) immediate hypersensitivity response with release of mediators responsible for bronchoconstriction. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hypersecretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is not mediated by IgE. 

Genetic alterations or abnormalities of germ cells, some of which can be caused by toxicant exposure, can be manifested by adverse effects on progeny. The important health effects of these kinds of alterations may be appreciated by considering the kinds of human maladies that are caused by inherited recessive mutations. One such disease is cystic fibrosis, in which the clinical phenotype has thick, dry mucus in the tubes of the respiratory system such that inhaled bacterial and fungal spores cannot be cleared from the system. This results in frequent, severe infections. It is the consequence of a faulty chloride transporter membrane protein that does not properly transport Cl ion from inside cells to the outside, where they normally retain water characteristic of healthy mucus. The faulty transporter protein is the result of a change of a single amino acid in the protein. 

Cell specializations include keratinized cells and ciliated cells. The keratinized epithelium contains the cytoskeletal protein keratin, and provides a tough impermeable barrier, mainly in the skin. Cihated cells have apical plasma membrane extensions composed of microtubules and are capable of beating rhythmically so as to move mucus or other substances through a duct. CiUa are common in the respiratory system. 

An example of an inhaled protein is DNase (Pulmozyme). It is an enzyme used to break down thick mucus secretions in the respiratory tracts of patients with cystic fibrosis. An inhaled protein that requires systemic... 

The initial step in the viral life cycle is the attachment of virus particles to the cell surface. Attachment is mediated by binding of the virus to a receptor. Sometimes co-receptors are also involved that might promote post-attachment events in the entry process. Receptor molecules are crmstituents of the cell membrane, and the receptor determinant, the stmcture to which the virus binds, may be either a protein epitope or the carbohydrate of a glycoprotein or a glycolipid. Soluble proteins present in body fluids and in mucus oti respiratory and enteric epithelia may also contain such carbohydrates and therefore interfere with virus binding to the cell siuface. 

The superficial layer is used to classify the stratification into simple, which consists of a single layer of cells, and stratified, which consists of more than one layer of cells. Stratified epithelium is usually composed of three layers. Cell division takes place in the basal cell layer (layer 1). Cells migrate and differentiate in the intermediate cell layer (layer 2) until they reach the superficial cell layer (layer 3). Specializations include keratinized and ciliated cells. Keratinized epithelium, which contains the cytoskeletal protein keratin and provides a tough impermeable barrier, occurs mainly in the skin. Ciliated cells have apical plasma membrane extensions composed of microtubules capable of beating rhythmically to move mucus or other substances through a duct. Cfiia are common in the respiratory system. 

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