Role of urothelial surface mucoprotein in intrinsic bladder defense

Shrom, Stanley H.; Parsons, C. Lowell; Mulholland, S. Grant

doi:10.1016/0090-4295(77)90245-x

Cited by 61 publications

(19 citation statements)

References 13 publications

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“…Consequently, the first line of host defense against UTI is concentrated on preventing UPEC adherence to the bladder mucosa. The luminal surface of the bladder is lined with highly sulfated and anionic glycosaminoglycans (GAGs) that contribute to bladder wall impermeability and afford an antimicrobial antiadherence property (120,158,196,197,199,237). Intuitively, urine flow seems to be a convenient defense mechanism; however, FimH binds to mannose moieties using "catch-bonds," interactions that are actually strengthened by the sheer stress induced during urine flow (257).…”

Section: Tactical Defensive Maneuvers: Host Factors To Prevent Upec Cmentioning

confidence: 99%

“…Uroplakins are partly responsible for the barrier function of the uroepithelium and act as receptors for FimH, the tip adhesin of UPEC type 1 fimbriae (298). For the purposes of this 120,158,196,197,199,237 THP Binds FimH, innate-adaptive signaling 172,190,192,193,195,225 Antimicrobial review, "postinoculation" and "infection" refer to E. coli accessing the urinary tract by the transurethral route, either experimentally in animals and volunteers or naturally in patients.…”

Section: Terrain: the Urinary Tractmentioning

confidence: 99%

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Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

2010

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Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden-a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses-from pattern receptor recognition to recruitment of phagocytic cells-that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity. MISSION: ERADICATE UPEC-MEDIATED UTIUrinary tract infection (UTI) is one of the most common infections in humans. Bacteria present in fecal matter inoculate the periurethral area, then the bladder (124, 176, 291), causing symptoms clinically termed cystitis. Left untreated, bacteria ascend the ureters to the kidney and establish a secondary infection, acute pyelonephritis. At this juncture, there is risk of permanent renal scarring, and bacteria can access the bloodstream (282). It is estimated that 40% of women and 12% of men will experience a symptomatic UTI, with incidences peaking in their early 20s or after age 85, respectively (75, 185). Approximately 25% of these women will experience recurrence within 6 to 12 months (75, 185). Uropathogenic Escherichia coli (UPEC) is the most common etiological agent responsible for uncomplicated UTI (93, 94,282). Uropathogenic strains are classified as extraintestinal pathogenic E. coli, a broad grouping of E. coli that cause diseases other than gastroenteritis and typically lack a type III secretion system (171,220,221,283,284). Nonetheless, UPEC strains express an assortment of virulence and fitness factors that aid in successful colonization of the mammalian urinary tract (126,136). In the United States alone, the estimated annual societal cost of UTI is more than 3 billion dollars (159).Despite a relatively in-depth knowledge base for UPEC physiology and virulence mechanisms (reviewed in references 54, 126, 136, and 284), no licensed vaccine to prevent UTI exists in the Un...

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Section: Tactical Defensive Maneuvers: Host Factors To Prevent Upec Cmentioning

confidence: 99%

Section: Terrain: the Urinary Tractmentioning

confidence: 99%

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

2010

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“…This mucin layer is thought to protect the bladder against pathogenic bacterial adherence and insult by noxious elements found in the urine. Disruption of this layer by acid treatment [13,16] or hormonal manipulation [13,24] has been shown to lead to a 20-to 100-fold increase in bacterial adsorption to bladder epithelial cells [19]. Furthermore, restoration of normal levels of bladder mucin is achieved within 24 h if left untreated or the mucin layer can be artificially restored with exogenous anionic polymers such as heparin or pentosan polysulfate [5].…”

Section: Discussionmentioning

confidence: 99%

Urinary tract glycoprotein: distribution and antigenic specificity

et al. 1994

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It has previously been demonstrated that the urinary tract contains a unique glycoprotein (GP1) that appears to serve a function in the clearance of pathogenic bacteria. We prepared a panel of monoclonal antibodies (mAbs) to human GP1 and examined its antigenic specificity and distribution in the human urinary tract. This was also observed in relation to another glycoprotein associated with infection, Tamm-Horsfall protein (THP), as well as to URO-5, a protein used in identifying the lower urinary tract. In enzyme-linked immunoadsorbent assays (ELISA), all of the GP1 mAbs reacted with GP1 prepared from both human urine and rabbit bladder mucosa. No immunoreactivity was observed with either THP mAbs or URO-5 mAbs. Western-blot analyses using GP1 mAbs with human urine GP1 preparations detected a single band of approximately 50-52 kDa. Human urinary tract tissues were also examined by immunohistochemical techniques using the GP1 mAbs, commercial THP, and URO-5 mAbs. In paraffin-embedded bladder sections, only GP1 mAbs reacted with the urothelium. Selective staining of distal collecting tubules, renal pelvis, and ureters was demonstrated for GP1 mAbs. Proximal convoluted tubules, loops of Henle, and Bowman's capsule failed to stain for GP1. In the same tissues, THP mAbs reacted with the thick and thin segments of medullary loops of nephrons (Henle's loops). URO-5 mAbs stained fresh frozen sections of bladder urothelium, distal collecting tubules, and portions of Henle's loops; however, they failed to stain paraffin-embedded tissue sections. These GP1 mAbs provide a new tool for biochemical and histochemical investigations of the mucin layer in both healthy and diseased urinary tract tissue.

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“…Acid treatment has been shown to remove the PAS-positive sialomucin layer while main taining the cellular integrity of the urothelium [7,14].…”

Section: Resultsmentioning

confidence: 99%

Heparin - an Examination of Its Antibacterial Adsorption Properties

Hanno¹,

Fritz²,

Mulholland³

et al. 1981

Eur Urol

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One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of innoculated bacteria. Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this ‘antiadherence factor’. To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy. Protamine offered no protection against bacterial adherence in the rabbit model. It appears that heparin’s protective effect is unrelated to its action as an anticoagulant.

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Role of urothelial surface mucoprotein in intrinsic bladder defense

Cited by 61 publications

References 13 publications

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

Urinary tract glycoprotein: distribution and antigenic specificity

Heparin - an Examination of Its Antibacterial Adsorption Properties

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