Phosphatidylcholine as a constituent in the colonic mucosal barrier—Physiological and clinical relevance

Ehehalt, Robert; Braun, Annika; Karner, Max; Füllekrug, Joachim; Stremmel, Wolfgang

doi:10.1016/j.bbalip.2010.05.014

Cited by 75 publications

(54 citation statements)

References 180 publications

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“…Previous studies have demonstrated that paracellular leakage caused by damage to the intracellular junctions may be an important mechanism underlying RV-associated diarrhea (20,28). Tight junctions have a key role in the association of cells (25)(26)(27)29) and in recent years, claudin-1 has been proposed as an important component of the tight junctions in the intestinal barrier (30,31). However, claudin-1 expression levels increase, rather than decrease, with increasing inflammatory intestinal permeability (25,26).…”

Section: Discussionmentioning

confidence: 99%

Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

Lei

Shi

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the effects of lactadherin on plasma D-lactic acid and small intestinal mucin (MUC) 2 and claudin-1 expression levels in rats with diarrhea induced by rotavirus (RV) infection. A total of 75 seven-day-old healthy Sprague-Dawley rats were randomly divided into the following five groups: Control (C), RV infection (RVI), lactadherin before rotavirus infection (LBRI), lactadherin after rotavirus infection (LARI), and blank (B). On day 4 of artificial feeding, the rats in groups RVI, LBRI and LARI were intragastric administered 1x10 6 PFU RV; whereas the rats in groups C and B were intragastrically administered an equal volume of maintenance solution from the RV supernatant and normal saline, respectively. In the LBRI and LARI groups, rats received daily intragastric administration of 0.25 mg lactadherin for three days prior to and following infection with RV, respectively. The course of diarrheal symptoms was observed in each group and samples were collected on days 1, 4, and 7 post-infection in order to determine the mucosal morphology, plasma D-lactic acid levels and the expression levels of MUC2 and the intracellular junction protein, claudin-1, in the small intestine. On day 4 post-infection, the rats in group RVI demonstrated severely damaged small intestines and typical diarrheal characteristics, as detected by light microscopy; whereas rats in groups LBRI and LARI demonstrated intact small intestinal villi with partial vacuolation of epithelial cells and changes in the position of their nuclei. Electron microscopy demonstrated that the rats in the RVI group had sparse, shortened, disordered intestinal microvilli and widened intercellular junctions; whereas those in groups LBRI and LARI had long intestinal microvilli sparser compared with groups B and C and slightly widened intercellular junctions. Plasma D-lactic acid levels were increased in groups RVI, LBRI and LARI, as compared with groups B and C, and the greatest levels were detected in the RVI group on days 1, 4 and 7 post-infection. In addition to maintaining intestinal permeability, lactadherin enhanced the expression levels of MUC2 and reduced the expression of claudin-1; therefore, further protecting the intestinal epithelial barrier, which may contribute to the prevention and treatment of diarrhea induced by infection with RV.

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Section: Discussionmentioning

confidence: 99%

Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

Lei

Shi

et al. 2016

Experimental and Therapeutic Medicine

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“…Reduction in the content of PC aa in the gastrointestinal mucosae leads to increased invasion of pathogens (118). PC aa derivatives in the plasma membrane inhibit actin polymerization, inhibit phagosomal actin assembly, stimulate Mycobacterium survival in phagosomes, and increase nitric oxide production (78,118,119).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Harrison

Dubois

John-Williams

et al. 2016

Molecular & Cellular Proteomics

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A thorough understanding of the molecular details of the interactions between bacteria and host are critical to ultimately prevent disease. Recent technological advances allow simultaneous analysis of host and bacterial protein and metabolic profiles from a single small tissue sample to provide insight into pathogenesis. We used the chinchilla model of human otitis media to determine, for the first time, the most expansive delineation of global changes in protein and metabolite profiles during an experimentally induced disease. After 48 h of infection with nontypeable Haemophilus influenzae, middle ear tissue lysates were analyzed by high-resolution quantitative two-dimensional liquid chromatography-tandem mass spectrometry. Dynamic changes in 105 chinchilla proteins and 66 metabolites define the early proteomic and metabolomic signature of otitis media. Our studies indicate that establishment of disease coincides with actin morphogenesis, suppression of inflammatory mediators, and bacterial aerobic respiration. We validated the observed increase in the actin-remodeling complex, Arp2/3, and experimentally showed a role for Arp2/3 in nontypeable Haemophilus influenzae invasion. Direct inhibition of actin branch morphology altered bacterial invasion into host epithelial cells, and is supportive of our efforts to use the information gathered to modify outcomes of disease. The twenty-eight nontypeable Haemophilus influenzae proteins identified participate in carbohydrate and amino acid metabolism, redox homeostasis, and include cell wall-associated metabolic proteins. Quantitative characterization of the molecular signatures of infection will redefine our understanding of host response driven developmental changes during pathogenesis. These data represent the first comprehensive study of host protein and metabolite profiles in vivo in response to infection and show the feasibility of extensive characterization of host protein profiles during disease. Identification of novel protein targets and metabolic biomarkers will advance development of therapeutic and diagnostic options for treatment of disease. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.052498, 1117-1138, 2016.Our current understanding of the global changes that occur during infection is primarily based upon transcriptional profiles of either the host or the bacteria. However, a significant component of disease progression is dependent upon posttranscriptional processes. Recent advances in the application of two-dimensional tandem mass spectrometry have dramatically increased sensitivity to allow simultaneous analyses of multiple molecules from very small biological samples. In this study, we report the comprehensive proteomic and metabolomic profiling of middle ear tissues using samples that are smaller than those typically obtained from a human biopsy. Proteomic and metabolomic analyses of samples as small as biopsies will revolutionize the elucidation of the mechanisms From the

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“…The gel-forming glycoprotein mucins form the main body of the mucus layer, consisting of a dense adherent layer (~116 µm) and a loose outer layer [35,36]. Whereas surface active lipids, or phospholipids, form a hydrophobic barrier at the luminal surface of colon to protect tissue from the high concentration of water-soluble toxins and bacterial products in the lumen [37,38]. The mucosal surface of colon is highly hydrophobic [39].…”

Section: Discussionmentioning

confidence: 99%

In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy

Ding

Dupont

Singhal

et al. 2017

Biomed. Opt. Express

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Abstract:The goal of this study is to evaluate endoscopic Raman spectroscopy as a noninvasive technique to determine histological inflammatory status of colitis. Colon mucosal composition was investigated in vivo from patients with ulcerative colitis (UC) and from ageand body mass index (BMI) matched controls using endoscope-coupled Raman spectroscopy. The results were co-registered with histological assessment of inflammatory status at the same locations. Substantial decreases (50-60%) in the content of phosphotidylcholines (PCs) and total lipids were observed in inflamed colon tissue (histology grade 1, 2 and 3) compared to those from the quiescent (histology grade 0) and from the controls. No significant difference was observed in lipids or PC contents between control and grade 0, or among grades 1 -3. The degree of lipid unsaturation increased in the inflamed tissue regardless of disease severity. The inflammation-associated alterations in lipids and PC are observed independent of BMI or the anatomical locations for data collection. Multivariate analysis using support vector machine (SVM) algorithm classified the spectra of the controls or the inactive colitis from those of inflamed tissue with a sensitivity of 83.5% and 97.1% respectively. Our results showed that mucosal lipid content is related to the microscopic disease activity, and thus could serve as a valuable spectral marker to differentiate active colitis from the quiescent. References and links1. E. V. Loftus, Jr., "Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences," Gastroenterology 126(6), 1504-1517 (2004). 2. J. Misiewicz, J. Lennard-Jones, A. Connell, J. Baron, and F. A. Jones, "Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis," Lancet 285(7378), 185-188 (1965

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Phosphatidylcholine as a constituent in the colonic mucosal barrier—Physiological and clinical relevance

Cited by 75 publications

References 180 publications

Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy

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