Progression of bacterial infections studied in real time ? novel perspectives provided by multiphoton microscopy

Månsson, Lisa; Melican, Keira; Molitoris, Bruce A.; Richter‐Dahlfors, Agneta

doi:10.1111/j.1462-5822.2007.01019.x

Cited by 32 publications

(28 citation statements)

References 56 publications

(83 reference statements)

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“…60 Albumin uptake by nonselective fluidphase endocytosis is probably a quantitatively important process in PTCs, as shown by the rapid cellular uptake of molecules not having receptors on the apical membrane, such as neutral fluorescent dextrans (markers of fluid-phase endocytosis). 61,62 The endocytic apparatus is found throughout the PT, although clathrincoated pits and vesicles are notably fewer in the S3 segment. 63 Expectedly, protein reabsorption and degradation are greatest in the S1 segment of the PTCs and least in the S3 segment.…”

Section: Endocytosis By the Ptmentioning

confidence: 99%

The Proximal Tubule and Albuminuria

Dickson

Wagner

Sandoval

et al. 2014

Journal of the American Society of Nephrology

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220

225

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Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apical membrane has been implicated as the "receptor" mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing "altered" albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism. Although the importance of urinary albumin in disease progression is known, the key mechanisms mediating the presence and toxic effects of albuminuria remain to be determined. Recently, the quantitative role of the glomerular filtration barrier (GFB) and the proximal tubule (PT) cell (PTC) in the development of albuminuria has been reexamined. Different lines of evidence, from multiple investigative teams, now suggest that the filtration of albumin, under physiologic conditions, is greater than previously determined. These data suggest an increased clinical role for the PT in minimizing albuminuria through the reabsorption of albumin. Emerging data also suggest that both glomerular permeability and PTCs play fundamental, physiologic, synergistic, interactive, and dynamic roles in the renal handling of albumin. Furthermore, it appears that PTCs, especially in the S1 segment, have specific mechanisms for efficiently and effectively reabsorbing and transcytosing albumin (reclamation). Therefore, the purpose of this review is to describe the emerging data regarding PTC albumin handling and provide a framework for considering future exciting, insightful, and novel studies with direct clinical relevance.This review is not intended to debate the important role of the GFB but to emphasize that the PT should be considered important both under physiologic and pathologic conditions. We believe that glomerular or PTC defects can and do result in proteinuria. Specifically, we outline current data supporting PT uptake of albumin and mechanisms of reabsorption and transcytosis, and we propose a mechanism for intracellular sorting between degradation and transcytotic pathways based on pH-dependent binding. DYSFUNCTIONAL PTCS LE...

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Section: Endocytosis By the Ptmentioning

confidence: 99%

The Proximal Tubule and Albuminuria

Dickson

Wagner

Sandoval

et al. 2014

Journal of the American Society of Nephrology

Self Cite

220

225

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“…Unfortunately, use of GFP is restricted to only those bacterial species that can produce the fluorescent protein, which eliminates the tracking of some key pathogens, such as S. epidermidis or obligates anaerobes. Månsson et al (2007) reports on the application of multiphoton microscopy for non-invasive in vivo imaging of ongoing infection. E. coli (GFP) uropathogenic strains were injected by micropuncture directly into the proximal tubule of a nephron in an exteriorized kidney.…”

Section: Detecting Medical Biofilmsmentioning

confidence: 99%

Medical biofilms

Bryers

2008

Biotech & Bioengineering

641

515

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For more than two decades, Biotechnology and Bioengineering has documented research focused on natural and engineered microbial biofilms within aquatic and subterranean ecosystems, wastewater and waste-gas treatment systems, marine vessels and structures, and industrial bioprocesses. Compared to suspended culture systems, intentionally engineered biofilms are heterogeneous reaction systems that can increase reactor productivity, system stability, and provide inherent cell:product separation. Unwanted biofilms can create enormous increases in fluid frictional resistances, unacceptable reductions in heat transfer efficiency, product contamination, enhanced material deterioration, and accelerated corrosion. Missing from B&B has been an equivalent research dialogue regarding the basic molecular microbiology, immunology, and biotechnological aspects of medical biofilms. Presented here are the current problems related to medical biofilms; current concepts of biofilm formation, persistence, and interactions with the host immune system; and emerging technologies for controlling medical biofilms.

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“…The use of a live animal model also brings with it the complications involved in maintaining true physiological conditions. Anesthesia levels, body temperature and fl uid levels are just a few of the physiological factors which must be monitored and maintained and this requires a wide range of expertise [82] . Much research is underway to address a number of these issues but until defi nitive results are obtained these issues must still be taken into account during experimental planning.…”

Section: Urinary Tract Infectionsmentioning

confidence: 99%