Secreted effectors of the innate mucosal barrier
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Nonstructural components of the mucosal barrier, including mucus produced by goblet cells and antimicrobial peptides produced by Paneth cells, play a fundamental role in mucosal protection. Goblet and Paneth cells arise from steM cell progenitors through intricate developmental pathways involving both Wnt and Notch signaling. Mucus, produced by goblet cells, protects the intestinal mucosal surface through its biophysical properties as well as its effects on luminal bacteria. The composition of mucus includes various mucins that are complex glycoproteins. Paneth cell products include antimicrobial peptides such as defensins, which influence the composition of the gut microbiota. Together, mucins and antimicrobial peptides form a secreted mucosal barrier that provides protection against an array of microbes. Components of both the innate and adaptive mucosal immune systems contribute to goblet cell and Paneth cell regulation in response to specific environmental challenges. Goblet cells are also involved in antigen transfer to antigen-presenting cells establishing appropriate regulatory and adaptive mucosal immune responses. Defects in either goblet or Paneth cells can lead to a disruption of the secreted mucosal barrier and thus contribute to the pathogenesis of mucosal diseases such as inflammatory bowel disease and necrotizing enterocolitis.
Future perspectives in peritoneal malignancy
Tom Cecil, John Bunni, Akash Mehta in A Practical Guide to Peritoneal Malignancy, 2019
The definition of pseudomyxoma peritonei (PMP) refers to the intraperitoneal accumulation of mucin secondary to mucinous neoplasia that is characterised by the redistribution phenomenon [6]. Most cases of PMP originate from a perforated mucinous tumour of the appendix, but mucinous neoplasms from other organs, such as the ovary, colon, pancreas and urachus can cause PMP [7]. PMP is characterised by slow and relentless growth confined mostly to the peritoneal cavity [6, 7]. PMP's distinguishing feature is the redistribution phenomenon that involves redistribution of the mucin within the intraperitoneal cavity as it follows the normal flow of the peritoneal fluid [8]. Common sites of mucin accumulation include the pelvis, paracolic gutters, liver capsule and omentum [7]. Hence, the PMP syndrome involves the formation of omental cake, mucinous ascites, peritoneal implants and ovarian involvement [6,7].
Respiratory System
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
The mucins are the major macromolecular components of the airway mucous layer and are the combined product of the secretion of epithelial goblet cells and the submucosal glands (Heidsiek et al. 1987). Acid and neutral mucins may be detected by using combined alcian blue (pH 2.5)/periodic acid-Schiff histochemistry, and sulfated mucins may be detected by high iron diamine histochemistry (Myers et al. 2008). The protein backbones of mucin glycoproteins may also be detected by IHC, or the MUC gene mRNAs that encode them may be investigated by Northern blot or in situ hybridization. There is evidence in rats that mucous flow in the nasal cavity of older animals is slower than it is in the young. This has implications for particle retention and susceptibility to toxicity (Gross et al. 1987). In addition to providing a physical barrier and contributing to the mucociliary escalator, mucins provide specific protection to the respiratory system via influenza virus aggregation and hemagglutinin inhibition and by reducing the respiratory burst of neutrophils (White et al. 2005a,b).
Oral delivery of biomacromolecules by overcoming biological barriers in the gastrointestinal tract: an update
Published in Expert Opinion on Drug Delivery, 2023
Shiyun Liu, Xiangce Wen, Xin Zhang, Shirui Mao
Mucus is predominantly composed of 95% water, 0.2–5.0% mucin, 0.5% globular protein, 0.5–1.0% electrolytes, 1–2% lipid, and DNA. Mucin is the functional component of the mucus layer that affects the penetration ability of drug carriers, which is mainly secreted by foveolar and goblet cells. In the stomach, the major mucins are MUC1, MUC5AC, and MUC6, whereas MUC2 is predominantly located in the small intestine. As a key component of the mucus layer, it contributes to the gelling of mucus as well as increasing its viscosity. The molecule weight of mucin ranges from 0.2 to 40 MDa, and it has the ability to form crosslinked and entangled fibrous networks. Mucin is mainly composed of protein backbone chains with repeating units of the PTS amino acids (proline, threonine, and serine) and carbohydrate side chains [31]. Mucin’s non-glycosylated backbone is linked by disulfide bonds that are essential for maintaining the network structure. The glycosylation repeating sequences of threonine, proline and serine domains, carboxyl and sulfate groups, and terminal sialic acid residues in the mucin endow the mucus with a negative charge environment. Due to electrostatic interactions, mucus is able to directly capture positively charged carriers, resulting in poor muco-penetration. The hydrophobic and hydrophilic regions of mucins also permit multiple interactions to trap nanocarriers in the mucus.
Impact of quorum sensing signaling molecules in gram-negative bacteria on host cells: current understanding and future perspectives
Published in Gut Microbes, 2022
Yingping Xiao, Huicong Zou, Jingjing Li, Tongxing Song, Wentao Lv, Wen Wang, Zhenyu Wang, Shiyu Tao
The gut<apos;>s first line of defense against invasion of pathogenic microorganisms and harmful metabolites is the mucus layer that covers the outer side of intestinal epithelial cells.145,146 The main component of the mucus layer is mucin, which is synthesized and secreted by intestinal goblet cells and acts as a barrier covering the entire intestinal surface.147–149 Studies have shown that the absence or abnormal expression of mucins can lead to intestinal diseases, whereas pathogenic microorganisms and some of their metabolites can induce abnormal expression of mucins.150–152 As for the influence of AHL on the intestinal mucus barrier, we first established a co-culture model of 3-oxo-C12-HSL and intestinal goblet cells, and demonstrated that 3-oxo-C12-HSL induced an imbalance of intestinal goblet cell homeostasis by causing mitochondrial swelling, mitochondrial membrane potential depolarization, mitochondrial dysfunction, and cell apoptosis. Furthermore, 3-oxo-C12-HSL inhibits mucin synthesis and sulfuration, ultimately destroying the intestinal mucus barrier. On this basis, the 3-oxo-C12-HSL/PON2 specific inhibitor/intestinal goblet cell co-culture model was established, and it was found that 3-oxo-C12-HSL induced a series of harmful biological effects in a PON2-dependent manner, eventually resulting in the disorder of intestinal goblet cell structure and function 85,153,154 (Figure 3).
The role of CFTR channel in female infertility
Published in Human Fertility, 2022
Mahmoud M. Habibullah
The earliest link of a role for mucin in female reproductive system is a report from 1998 documenting that Muc1 mRNA and protein expression is regulated by ovarian steroid hormones in mice (Carson et al., 1998). A more recent study used proteomic analysis to identify more than 200 proteins including MUC1, MUC5AB, MUC5C, and MUC16 to be highly secreted in cervical mucosa during ovulation (Andersch-Björkman et al., 2007). Cervical mucus production during ovulation is characterised by increased glycosylated oligosaccharides; a pattern that changes during the menstrual cycle (Pluta et al., 2011). The function of the glycosylated mucins may be to retain water in the cervical canal to allow sperm migration during ovulation. However, in CF, this may be problematic as discussed below.
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