Bactericidal properties of murine intestinal phospholipase A2.

Harwig, Sylvia S.L.; Tan, Leonie; Qu, Xiao; Cho, Yoon; Eisenhauer, Patricia B.; Lehrer, Robert I.

doi:10.1172/jci117704

Cited by 237 publications

(156 citation statements)

References 55 publications

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“…We propose that PA colonization improves this elimination by increasing sPLA2-IIA expression of airways cells. In agreement, previous studies showed that sPLA2-IIA is present in human and animal biological fluids or cell supernatants at sufficient levels to kill bacteria 21,[53][54][55][56] . AMPs such as LL-37 have also been shown to play a role in pulmonary host defense toward SA and PA in CF lungs 57 , although the antimicrobial activity of these AMPs is impaired in CF airways [57][58][59] .…”

Section: Discussionsupporting

confidence: 91%

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

et al. 2014

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Young cystic fibrosis (CF) patients' airways are mainly colonized by Staphylococcus aureus, while Pseudomonas aeruginosa predominates in adults. However, the mechanisms behind this infection switch are unclear. Here, we show that levels of type-IIA-secreted phospholipase A2 (sPLA2-IIA, a host enzyme with bactericidal activity) increase in expectorations of CF patients in an age-dependent manner. These levels are sufficient to kill S. aureus, with marginal effects on P. aeruginosa strains. P. aeruginosa laboratory strains and isolates from CF patients induce sPLA2-IIA expression in bronchial epithelial cells from CF patients (these cells are a major source of the enzyme). In an animal model of lung infection, P. aeruginosa induces sPLA2-IIA production that favours S. aureus killing. We suggest that sPLA2-IIA induction by P. aeruginosa contributes to S. aureus eradication in CF airways. Our results indicate that a bacterium can eradicate another bacterium by manipulating the host immunity.

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Section: Discussionsupporting

confidence: 91%

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

et al. 2014

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“…This molecule has proinflammatory and bactericidal activity (35) and has been isolated in the inflamed mucosa of patients suffering from inflammatory bowel disease (36) as well as in the circulation of patients suffering from septic shock (37). We quantified phospholipase A 2 in the intestinal mucosa and in the intestinal fluid of the CD14-blocked and control rabbits exposed to Shigella, but found no differences between the two groups of rabbits with respect to secretory phospholipase quantities (data not shown).…”

Section: Discussionmentioning

confidence: 97%

Blockade of CD14 Increases Shigella-Mediated Invasion and Tissue Destruction

Wennerås

Avé

Huerre

et al. 2000

The Journal of Immunology

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Shigella is a diarrheal pathogen that causes disease through invasion of the large intestinal mucosa. The endotoxin of the invading bacterium may play a key role in the disease process by causing inflammation and tissue injury during infection. Earlier studies have shown that various animal species lacking functional CD14 were protected against endotoxin-mediated shock. Rabbits experimentally infected with Shigella were used to test the hypothesis that blockade of endotoxin-induced cell activation with anti-CD14 mAb would diminish inflammation and thus disease severity. Unexpectedly, we observed that the intestinal mucosa of anti-CD14-treated animals exhibited a 50-fold increase in bacterial invasion and more severe tissue injury compared with controls. Despite higher bacterial loads in treated animals, the numbers of polymorphonuclear leukocytes that were recruited to the infection site were similar to those in controls. Furthermore, the phagocytic cells of CD14-blocked animals produced IL-1 and TNF-α. Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment interfered with host defense mechanisms involved with removal/eradication of Shigella.

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“…PGLYRPs require Ca 2ϩ and N-glycosylation for bactericidal activity, which are not usually required by membrane-permeabilizing antibacterial peptides, such as defensins or magainin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). PGLYRPs are bactericidal (kill 99% of bacteria) at 0.1-1 M, and thus are more active than most antibacterial peptides, such as defensins or magainin (1-6, 37), but less active than phospholipase A 2 , which is the most active human bactericidal peptide (1-4, 7).…”

Section: Discussionmentioning

confidence: 99%

“…Besides forming a mechanical barrier, these tissues and their secretions are rich in antimicrobial peptides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), including defensins (1-6), phospholipase A 2 (7), dermicidin (8), cathelicidin (9), RNases (10), and psoriasin (11). Antimicrobial peptides are low molecular weight amphipathic molecules that kill microorganisms by damaging their membranes (1)(2)(3)(4).…”

mentioning

confidence: 99%

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

Wang

et al. 2006

Journal of Biological Chemistry

195

298

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Skin and mucous membranes come in contact with external environment and protect tissues from infections by producing antimicrobial peptides. We report that human peptidoglycan recognition proteins 3 and 4 (PGLYRP3 and PGLYRP4) are secreted as 89 -115-kDa disulfide-linked homo-and heterodimers and are bactericidal against several pathogenic and nonpathogenic transient, but not normal flora, Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also bacteriostatic toward all other tested bacteria, which include Gram-negative bacteria and normal flora Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also active in vivo and protect mice against experimental lung infection. In contrast to antimicrobial peptides, PGLYRPs kill bacteria by interacting with their cell wall peptidoglycan, rather than permeabilizing their membranes. PGLYRP3 and PGLYRP4 are expressed in the skin, eyes, salivary glands, throat, tongue, esophagus, stomach, and intestine. Thus, we have identified the function of mammalian PGLYRP3 and PGLYRP4, and show that they are a new class of bactericidal and bacteriostatic proteins that have different structures, mechanism of actions, and expression patterns than antimicrobial peptides.

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Bactericidal properties of murine intestinal phospholipase A2.

Cited by 237 publications

References 55 publications

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

Blockade of CD14 Increases Shigella-Mediated Invasion and Tissue Destruction

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

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