Antimicrobial Peptides in the Airway

Laube, D. M.; Yim, Sunghan; Ryan, Lisa K.; Kisich, Kevin O.; Diamond, Gill

doi:10.1007/3-540-29916-5_6

Cited by 97 publications

(112 citation statements)

References 145 publications

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“…The sAMPs play a pivotal role in maintaining mucosal immune integrity (Allgrove et al 2008;Bals and Hiemstra 2004;Papacosta and Nassis 2011;West et al 2006) by working synergistically to curtail invading bacteria, viruses, and fungi (De Smet and Contreras 2005;Radek and Gallo 2007;West et al 2006) and are vital in both the prevention and clearance of many types of infection (Bowdish et al 2005;Davison et al 2009;West et al 2006). In particular, infections of the oral cavity and upper respiratory tract (URTI) are associated with depressed levels of sAMPs (Table 1) (Bartlett et al 2008;Bishop and Gleeson 2009;Dale et al 2006;Doss et al 2010;Laube et al 2006;Putsep et al 2002;Tanida et al 2003;Tao et al 2005;Ueta et al 2000;West et al 2006), highlighting their prominent role in first--line immune defense.…”

Section: Introductionmentioning

confidence: 99%

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise

et al. 2015

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Section: Introductionmentioning

confidence: 99%

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise

et al. 2015

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“…In the mammalian respiratory system, the interface between the environment and the organism is a thin layer of airway surface liquid (ASL). To maintain sterile lungs and protect against bombardment with bacteria, mammalian lungs have evolved multiple protective mechanisms, one of which is antimicrobials in ASL that rapidly kill inhaled and aspirated bacteria (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

Alaiwa¹,

Reznikov²,

Gansemer³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

181

162

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The pulmonary airways are continuously exposed to bacteria. As a first line of defense against infection, the airway surface liquid (ASL) contains a complex mixture of antimicrobial factors that kill inhaled and aspirated bacteria. The composition of ASL is critical for antimicrobial effectiveness. For example, in cystic fibrosis an abnormally acidic ASL inhibits antimicrobial activity. Here, we tested the effect of pH on the activity of an ASL defensin, human β-defensin-3 (hBD-3), and the cathelicidin-related peptide, LL-37. We found that reducing pH from 8.0 to 6.8 reduced the ability of both peptides to kill Staphylococcus aureus. An acidic pH also attenuated LL-37 killing of Pseudomonas aeruginosa. In addition, we discovered synergism between hBD-3 and LL-37 in killing S. aureus. LL-37 and lysozyme were also synergistic. Importantly, an acidic pH reduced the synergistic effects of combinations of ASL antibacterials. These results indicate that an acidic pH reduces the activity of individual ASL antimicrobials, impairs synergism between them, and thus may disrupt an important airway host defense mechanism.

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“…Lung bronchoalveolar space contains a variety of molecules with antibacterial properties, such as lactoferrin, complement, collectins or surfactant proteins, and antimicrobial peptides (AMPs), particularly cationic AMPs (CAMPs), such as cathelicidins and ␤-defensins (37,67,70). Here we investigated the effect of airway antimicrobial molecules on Y. pestis and observed killing effects of rat bronchoalveolar lavage fluid (rBALF), mediated by AMPs.…”

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confidence: 99%

“…Y. pestis is susceptible to the pulmonary CAMPs cathelicidin LL-37 and rCRAMP. The cathelicidins and defensins are considered to be the major AMPs for host lung defense and are detectable in BALF (2,37). A cathelicidin (LL-37 in humans and rCRAMP in rats) and ␤-defensin 1 (RBD-1 in rats) are both expressed constitutively in rodent lungs and human respiratory tract epithelial cells, with LL-37 being expressed specifically by pneumocytes (28,37,61,67).…”

mentioning

confidence: 99%

“…The cathelicidins and defensins are considered to be the major AMPs for host lung defense and are detectable in BALF (2,37). A cathelicidin (LL-37 in humans and rCRAMP in rats) and ␤-defensin 1 (RBD-1 in rats) are both expressed constitutively in rodent lungs and human respiratory tract epithelial cells, with LL-37 being expressed specifically by pneumocytes (28,37,61,67). In this study, the antimicrobial activity of the isolated small-peptide fraction of rBALF was not affected by DTT (data not shown), a treatment previously shown to disrupt the disulfide bridges of the defensins (31,60).…”

mentioning

confidence: 99%

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Capsular Antigen Fraction 1 and Pla Modulate the Susceptibility of Yersinia pestis to Pulmonary Antimicrobial Peptides Such as Cathelicidin

2008

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Inhaled Yersinia pestis produces a severe primary pneumonia known as pneumonic plague, which is contagious and highly lethal to humans and animals. In this study, we first determined the susceptibility of Y. pestis KIM6 to antimicrobial molecules of the airways. We found that (i) rat bronchoalveolar lavage fluid (rBALF) effectively killed KIM6 cells growing at 37°C; (ii) the antibacterial components of rBALF were small peptides (<10 kDa) that included two cationic antimicrobial peptides (CAMPs), the rat cathelicidin rCRAMP, and ␤-defensin RBD-1; (iii) the human cathelicidin LL-37 killed KIM6 cells as well as rBALF did; and (iv) the bactericidal property of LL-37 was synergistically amplified by human ␤-defensin 1, another constitutively expressed pulmonary CAMP. Second, the effects of three major surface proteins of Y. pestis, namely, the capsular antigen fraction 1 (F1), the pH 6 antigen (Psa fimbriae), and the outer membrane protease Pla, on the bactericidal effect of the antimicrobial rBALF peptides was determined with corresponding deletion mutants. We showed that (i) a Y. pestis psa mutant was only slightly more susceptible to rBALF than the parental KIM6 strain, (ii) a caf (F1 gene) mutant and a caf psa mutant were resistant to rBALF or LL-37, (iii) a caf pla mutant was as susceptible to the effect of rBALF or LL-37 as KIM6 was (caf ؉ pla ؉ ), and (iv) only the single caf mutant (pla ؉ ), but not KIM6 or the caf pla double mutant, degraded LL-37. The activity of Pla toward LL-37 was confirmed with pla mutants carrying a single-residue substitution affecting plasminogen cleavage. Taken together, our data indicated that Pla might act as a virulence factor not only by processing plasminogen but also by inactivating CAMPs, particularly when F1 is not expressed.

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Antimicrobial Peptides in the Airway

Cited by 97 publications

References 145 publications

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

Capsular Antigen Fraction 1 and Pla Modulate the Susceptibility of Yersinia pestis to Pulmonary Antimicrobial Peptides Such as Cathelicidin

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