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The First Line of Defense

View Article: PubMed Central

ABSTRACT

Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen. The intestinal barrier is compromised following alcohol exposure, which can lead to life-threatening systemic complications including sepsis and multiple organ failure. Furthermore, alcohol is a major confounding factor in pathology associated with trauma. Experimental data from both human and animal studies suggest that alcohol perturbs the intestinal barrier and its function, which is exacerbated by a “second hit” from traumatic injury. This article highlights the role of alcohol-mediated alterations of the intestinal epithelia and its defense against bacteria within the gut, and the impact of alcohol on intestinal immunity, specifically on T cells and neutrophils. Finally, it discusses how the gut microbiome both contributes to and protects the intestines from dysbiosis after alcohol exposure and trauma.

No MeSH data available.


Related in: MedlinePlus

Intestinal epithelial-cell junctions. Contents within the intestinal lumen are prevented from passing between epithelial cells by apical tight-junction complexes. Tight junctions are composed of claudin proteins (blue) and regulated by occludin proteins (yellow). Claudin and occludin proteins are transmembrane proteins attached to an adaptor molecule, zonula occludins protein 1 (ZO-1) (purple), which anchors tight-junction proteins to intracellular actin (red). Alcohol causes disruption of occludin and ZO proteins by an unknown mechanism. Junctional adhesion molecules (JAMs) (green) also support tight-junction interactions. Intestinal epithelial cells are further supported by adherens molecules, including E-cadherins (pink), which also contribute to cell–cell contact. These junctions allow selective separation of the intestinal lumen (top) and lamina propria (bottom).
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f2-arcr-37-2-209: Intestinal epithelial-cell junctions. Contents within the intestinal lumen are prevented from passing between epithelial cells by apical tight-junction complexes. Tight junctions are composed of claudin proteins (blue) and regulated by occludin proteins (yellow). Claudin and occludin proteins are transmembrane proteins attached to an adaptor molecule, zonula occludins protein 1 (ZO-1) (purple), which anchors tight-junction proteins to intracellular actin (red). Alcohol causes disruption of occludin and ZO proteins by an unknown mechanism. Junctional adhesion molecules (JAMs) (green) also support tight-junction interactions. Intestinal epithelial cells are further supported by adherens molecules, including E-cadherins (pink), which also contribute to cell–cell contact. These junctions allow selective separation of the intestinal lumen (top) and lamina propria (bottom).

Mentions: The mucus layer is not impenetrable, however, and the tight junction complexes between the epithelial cells below the mucus layer play a crucial role in providing a second level of protection. Tight junctions (figure 2) are multi-protein complexes consisting of transmembrane, scaffold, and adaptor proteins, which play an indispensable part in the maintenance of barrier function (Ivanov 2012). The proteins of tight junctions form a paracellular seal and function as a selectively permeable barrier between adjacent epithelial cells. They allow nutrients from food to pass out of the lumen while blocking passage of bacteria. Among the transmembrane proteins making up tight junctions are occludin, claudins, tricellulin, and junctional adhesions (Ulluwishewa et al. 2011). Although the function of occludin proteins is unknown, they are not essential for tight junction formation but appear instead to be instrumental in the regulation of the junctions (Balda and Matter 2008; Forster 2008; Groschwitz and Hogan 2009). Claudins are a family of both tissue- and cell-type–specific proteins considered to be the main structural components of the tight junctions. A third class of proteins found in tight junctions are junction-associated adhesion molecules (JAMs); however, little is known about their contribution to tight junction function and assembly (Balda and Matter 2008; Forster 2008; Groschwitz and Hogan 2009).


The First Line of Defense
Intestinal epithelial-cell junctions. Contents within the intestinal lumen are prevented from passing between epithelial cells by apical tight-junction complexes. Tight junctions are composed of claudin proteins (blue) and regulated by occludin proteins (yellow). Claudin and occludin proteins are transmembrane proteins attached to an adaptor molecule, zonula occludins protein 1 (ZO-1) (purple), which anchors tight-junction proteins to intracellular actin (red). Alcohol causes disruption of occludin and ZO proteins by an unknown mechanism. Junctional adhesion molecules (JAMs) (green) also support tight-junction interactions. Intestinal epithelial cells are further supported by adherens molecules, including E-cadherins (pink), which also contribute to cell–cell contact. These junctions allow selective separation of the intestinal lumen (top) and lamina propria (bottom).
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590618&req=5

f2-arcr-37-2-209: Intestinal epithelial-cell junctions. Contents within the intestinal lumen are prevented from passing between epithelial cells by apical tight-junction complexes. Tight junctions are composed of claudin proteins (blue) and regulated by occludin proteins (yellow). Claudin and occludin proteins are transmembrane proteins attached to an adaptor molecule, zonula occludins protein 1 (ZO-1) (purple), which anchors tight-junction proteins to intracellular actin (red). Alcohol causes disruption of occludin and ZO proteins by an unknown mechanism. Junctional adhesion molecules (JAMs) (green) also support tight-junction interactions. Intestinal epithelial cells are further supported by adherens molecules, including E-cadherins (pink), which also contribute to cell–cell contact. These junctions allow selective separation of the intestinal lumen (top) and lamina propria (bottom).
Mentions: The mucus layer is not impenetrable, however, and the tight junction complexes between the epithelial cells below the mucus layer play a crucial role in providing a second level of protection. Tight junctions (figure 2) are multi-protein complexes consisting of transmembrane, scaffold, and adaptor proteins, which play an indispensable part in the maintenance of barrier function (Ivanov 2012). The proteins of tight junctions form a paracellular seal and function as a selectively permeable barrier between adjacent epithelial cells. They allow nutrients from food to pass out of the lumen while blocking passage of bacteria. Among the transmembrane proteins making up tight junctions are occludin, claudins, tricellulin, and junctional adhesions (Ulluwishewa et al. 2011). Although the function of occludin proteins is unknown, they are not essential for tight junction formation but appear instead to be instrumental in the regulation of the junctions (Balda and Matter 2008; Forster 2008; Groschwitz and Hogan 2009). Claudins are a family of both tissue- and cell-type–specific proteins considered to be the main structural components of the tight junctions. A third class of proteins found in tight junctions are junction-associated adhesion molecules (JAMs); however, little is known about their contribution to tight junction function and assembly (Balda and Matter 2008; Forster 2008; Groschwitz and Hogan 2009).

View Article: PubMed Central

ABSTRACT

Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen. The intestinal barrier is compromised following alcohol exposure, which can lead to life-threatening systemic complications including sepsis and multiple organ failure. Furthermore, alcohol is a major confounding factor in pathology associated with trauma. Experimental data from both human and animal studies suggest that alcohol perturbs the intestinal barrier and its function, which is exacerbated by a “second hit” from traumatic injury. This article highlights the role of alcohol-mediated alterations of the intestinal epithelia and its defense against bacteria within the gut, and the impact of alcohol on intestinal immunity, specifically on T cells and neutrophils. Finally, it discusses how the gut microbiome both contributes to and protects the intestines from dysbiosis after alcohol exposure and trauma.

No MeSH data available.


Related in: MedlinePlus