Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?

Nader, Helena B.; Sf, Chavante; Ea, dos-Santos; Tw, Oliveira; Jf, de-Paiva; Sm, Jerônimo; Gf, Medeiros; Lr, de-Abreu; El, Leite; Jf, de-Sousa-Filho; Ra, Castro; Toma, Leny; Tersariol, Ivarne L.S.; Ma, Porcionatto; Cp, Dietrich

doi:10.1590/s0100-879x1999000500005

Cited by 79 publications

(40 citation statements)

References 34 publications

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“…on May 10, 2018 by guest http://iai.asm.org/ main purpose of heparin is in a defensive mechanism at sites of tissue injury against invading bacteria and other foreign materials (36). HSPGs are attractive as therapeutic targets since a wide range of viral and bacterial pathogens are known to bind to HS chains (2,14,21,25), and our work further shows that the sulfate moieties of HSPGs function as P. aeruginosa-binding receptors.…”

Section: Discussionmentioning

confidence: 54%

Pseudomonas aeruginosa -Mediated Damage Requires Distinct Receptors at the Apical and Basolateral Surfaces of the Polarized Epithelium

2010

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Pseudomonas aeruginosa, an important opportunistic pathogen of humans, exploits epithelial damage to establish infection. We have rigorously explored the role of N-glycoproteins and heparan sulfate proteoglycans (HSPGs) in P. aeruginosa-mediated attachment and subsequent downstream events at the apical (AP) and basolateral (BL) surfaces of polarized epithelium. We demonstrate that the N-glycan chains at the AP surface are necessary and sufficient for binding, invasion, and cytotoxicity to kidney (MDCK) and airway (Calu-3) cells grown at various states of polarization on Transwell filters. Upregulation of N-glycosylation enhanced binding, whereas pharmacologic inhibition of N-glycosylation or infection of MDCK cells defective in N-glycosylation resulted in decreased binding. In contrast, at the BL surface, the HS moiety of HSPGs mediated P. aeruginosa binding, cytotoxicity, and invasion. In incompletely polarized epithelium, HSPG abundance was increased at the AP surface, explaining its increased susceptibility to P. aeruginosa colonization and damage. Using MDCK cells grown as three-dimensional cysts as a model for epithelial organs, we show that P. aeruginosa specifically colocalized with HS-rich areas at the BL membrane but with complex N-glycans at the AP surface. Finally, P. aeruginosa bound to HS chains and N-glycans coated on plastic surfaces, showing the highest binding affinity toward isolated HS chains. Together, these findings demonstrate that P. aeruginosa recognizes distinct receptors on the AP and BL surfaces of polarized epithelium. Changes in the composition of N-glycan chains and/or in the distribution of HSPGs may explain the enhanced susceptibility of damaged epithelium to P. aeruginosa.Ninety-five percent of all infectious agents enter through mucosal surfaces of the gastrointestinal, genitourinary, and respiratory tracts (reviewed in reference 35). These mucosal surfaces are usually lined by a single layer of epithelial cells, which serves as the primary barrier against the entry of most infectious agents and can be considered a primary component of the innate immune system. Epithelial cells form highly polarized cell layers with apical (AP) and basolateral (BL) surfaces that exhibit distinct protein, lipid, and glycoconjugate compositions. Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen of humans that exploits injured mucosa to cause acute and chronic infections with high morbidity and mortality (reviewed in references 26 and 31). In the setting of epithelial injury and immunocompromise, this Gram-negative pathogen causes serious infections in patients with extensive burns, corneal trauma, or catheter-related bladder injury or in those on ventilators. In addition, P. aeruginosa chronically colonizes the lungs of patients with cystic fibrosis (CF) (4), leading to severe pulmonary damage and death. Despite aggressive antibiotic therapy, the fatality rate for many P. aeruginosa infections is 40%, and new approaches to treatment are even more critical now that antibiotic resistance...

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Section: Discussionmentioning

confidence: 54%

Pseudomonas aeruginosa -Mediated Damage Requires Distinct Receptors at the Apical and Basolateral Surfaces of the Polarized Epithelium

2010

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“…Heparin and its close relative heparan sulfate, the natural anticoagulant of endothelium, have been maintained throughout evolution and, interestingly, are present in species without a coagulation system. 26 Similar to heparin or heparan sulfate, histones are highly evolutionarily conserved. Functionally, histones combine microbicidal 2 and cytotoxic functions 3 with prothrombotic properties.…”

Section: Discussionmentioning

confidence: 99%

Histones induce rapid and profound thrombocytopenia in mice

Fuchs

Bhandari

Wagner

2011

Blood

371

412

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“…We ascribed this antagonism to the formation of acid-base complexes between the basic myotoxins of the venoms and the polyanion compounds. There are reports suggesting that some heparinoids exhibit various biological functions (9,10) and among them, suramin, one of the oldest heparinoids, represents an important target molecule (11,12). Suramin is a polysulfonated naphthylamine-amine-benzamide derivative ( Figure 1) that has been widely used for more than fifty years in the treatment of onchocerciasis and trypanosomiasis (12)(13)(14).…”

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confidence: 99%

Effect of suramin on myotoxicity of some crotalid snake venoms

Arruda

Silva

Moraes

et al. 2002

Braz J Med Biol Res

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We investigated the protective effect of suramin, an enzyme inhibitor and an uncoupler of G protein from receptors, on the myotoxic activity in mice of different crotalid snake venoms (A.c. laticinctus, C.v. viridis, C.d. terrificus, B. jararacussu, B. moojeni, B. alternatus, B. jararaca, L. muta). Myotoxicity was evaluated in vivo by injecting im the venoms (0.5 or 1.0 mg/kg) dissolved in physiological saline solution (0.1 ml) and measuring plasma creatine kinase (CK) activity. Two experimental approaches were used in mice (N = 5 for each group). In protocol A, 1 mg of each venom was incubated with 1.0 mg suramin (15 min, 37ºC, in vitro), and then injected im into the mice at a dose of 1.0 mg/kg (in vivo). In protocol B, venoms, 1.0 mg/kg, were injected im 15 min prior to suramin (1.0 mg/kg, iv). Before and 2 h after the im injection blood was collected by orbital puncture. Plasma was separated and stored at 4ºC for determination of CK activity using a diagnostic kit from Sigma. Preincubation of some venoms (C.v. viridis, A.c. laticinctus, C.d. terrificus and B. jararacussu) with suramin reduced (37-76%) the increase in plasma CK, except for B. alternatus, B. jararaca or L. muta venoms. Injection of suramin after the venom partially protected (34-51%) against the myotoxicity of B. jararacussu, A.c. laticinctus and C.d. terrificus venom, and did not protect against C.v. viridis, L. muta, B. moojeni, B. alternatus or B. jararaca venoms. These results show that suramin has an antimyotoxic effect against some, but not all the North and South American crotalid snake venoms studied here.

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Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?

Cited by 79 publications

References 34 publications

Pseudomonas aeruginosa -Mediated Damage Requires Distinct Receptors at the Apical and Basolateral Surfaces of the Polarized Epithelium

Pseudomonas aeruginosa -Mediated Damage Requires Distinct Receptors at the Apical and Basolateral Surfaces of the Polarized Epithelium

Histones induce rapid and profound thrombocytopenia in mice

Effect of suramin on myotoxicity of some crotalid snake venoms

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