Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes

Levy, Ofer

doi:10.1189/jlb.0604320

Cited by 161 publications

(113 citation statements)

References 250 publications

(248 reference statements)

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“…Paneth cells, which are specialized secretor y enterocytes located at the base of small intestinal crypts, secrete lysozyme, phospholipase A2, and antimicrobial peptides (also secreted by absorptive enterocytes) that regulate composition and distribution of different bacterial populations [39,40] . Defensins (α and β) and cathelicidins are the two main families of antimicrobial peptides produced by intestinal cells [40] .…”

Section: Immature Intestinal Motility Digestion and Barrier Functionmentioning

confidence: 99%

Necrotizing enterocolitis: A multifactorial disease with no cure

Schnabl

Aerde²,

Thomson³

et al. 2008

WJG

161

120

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INTRODUCTIONNecrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates and remains one of the most common gastrointestinal emergencies in newborn infants [1] . Onset of NEC is often within the first three months of life and neonates who are of extremely low birth weight (< 1000 g) and under 28 wk gestation are the most susceptible [2] . Full term neonates account for 10% of all NEC cases while premature infants account for 90% [3] . With an incidence rate of 1%-5% for all newborns admitted to the NICU [1] , a prevalence of 7%-14% of very low birth weight infants (VLBW, 500-1500 g) [4] and a mortality rate approaching 20%-50% [5] , NEC continues to represent a significant clinical problem. In Canada, the incidence rate is 1.8 per 100 live births with a prevalence of 7% of VLBW infants [1] . Advances in obstetric and neonatal care have improved survival rates for smaller, more immature infants, and as more VLBW preterm infants survive the neonatal period, the population at risk for NEC increases [1] .No consistent association between sex, race, and rates of NEC has been identified. However, male VLBW infants and black infants are at greater risk of death [6] . Due to inadequate treatments and no effective preventative strategy, an estimated 20%-40% of babies with NEC require surgery [1] and 10%-30% experience significant morbidity including neurodevelopmental impairment, vision and hearing impairment, failure to thrive, feeding abnormalities, diarrhea, bowel obstruction, and short bowel syndrome [1,2,7] . The case fatality rate with surgical intervention is as high as 50% [1] . NEC is also a financial burden to the health care system with yearly hospital charges reported to be as high as $6.5 million in the US [8] . Thus, NEC continues to be an important health issue for preterm neonates. DIAGNOSIS Clinical signs and symptomsThe onset of NEC can occur suddenly within a few AbstractNecrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

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Section: Immature Intestinal Motility Digestion and Barrier Functionmentioning

confidence: 99%

Necrotizing enterocolitis: A multifactorial disease with no cure

Schnabl

Aerde²,

Thomson³

et al. 2008

WJG

161

120

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“…Plants, as well as animals, can defend themselves against pathogenic microbes via cationic antimicrobial proteins and peptides, which can kill micro-organisms without any harmful effect on the host (Hancock & Lehrer 1998;Levy, 2004;Brogden, 2005).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial activity of potato aspartic proteases (StAPs) involves membrane permeabilization

et al. 2006

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Solanum tuberosum aspartic proteases (StAPs) with antimicrobial activity are induced after abiotic and biotic stress. In this study the ability of StAPs to produce a direct antimicrobial effect was investigated. Viability assays demonstrated that StAPs are able to kill spores of Fusarium solani and Phytophthora infestans in a dose-dependent manner. Localization experiments with FITC-labelled StAPs proved that the proteins interact directly with the surface of spores and hyphae of F. solani and P. infestans. Moreover, incubation of spores and hyphae with StAPs resulted in membrane permeabilization, as shown by the uptake of the fluorescent dye SYTOX Green. It is concluded that the antimicrobial effect of StAPs against F. solani and P. infestans is caused by a direct interaction with the microbial surfaces followed by membrane permeabilization.

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“…In particular, LBP participates in the acute mobilization of circulating neutrophils to sites of tissue injury. Stored in the mobilized neutrophils, antimicrobial peptides and the bactericidal/ permeability-increasing protein (BPI) contribute to the elimination of bacteria (8,9). BPI, another LBP, is a 55-kDa cationic protein specifically active against Gram-negative bacteria.…”

mentioning

confidence: 99%

Evidence of a bactericidal permeability increasing protein in an invertebrate, theCrassostrea gigas Cg-BPI

González-Aravena

Gueguen

Destoumieux-Garzón

et al. 2007

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

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124

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A cDNA sequence with homologies to members of the LPS-binding protein and bactericidal/permeability-increasing protein (BPI) family was identified in the oyster Crassostrea gigas. The recombinant protein was found to bind LPS, to display bactericidal activity against Escherichia coli, and to increase the permeability of the bacterial cytoplasmic membrane. This indicated that it is a BPI rather than an LPS-binding protein. By in situ hybridization, the expression of the C. gigas BPI (Cg-bpi) was found to be induced in hemocytes after oyster bacterial challenge and to be constitutive in various epithelia of unchallenged oysters. Thus, Cg-bpi transcripts were detected in the epithelial cells of tissues/organs in contact with the external environment (mantle, gills, digestive tract, digestive gland diverticula, and gonad follicles). Therefore, Cg-BPI, whose expression profile and biological properties are reminiscent of mammalian BPIs, may provide a first line of defense against potential bacterial invasion. To our knowledge, this is the first characterization of a BPI in an invertebrate.antimicrobial ͉ epithelia ͉ hemocyte ͉ mollusk ͉ oyster innate immunity M arine invertebrates including bivalve mollusks have evolved in the continuous presence of microorganisms. The oysters, such as Crassostrea gigas, harbor a diverse microflora both on their surface (epibiosis) and inside the body cavities and hemolymph (endobiosis). They have developed an efficient immune system for maintaining balance with commensal and pathogenic bacteria, in particular with the Gram-negative Vibrio spp. abundant in their tissues/organs. LPS from Gram-negative bacteria play an important role in the interaction and activation of the innate immune system including the antimicrobial defense (1, 2). In invertebrates, LPSbinding proteins (LBP) participate in the transduction of cellular signals from LPS. LBPs have been characterized in the freshwater crayfish Pacifastacus leniusculus (3), the shrimp Litopenaeus stylirostris (4), the earthworm Eisenia foetida (5), and the silkworm Bombyx mori (6). In mammals, LBP is an acute phase plasma protein constitutively secreted by liver that induces cellular responses (7). In particular, LBP participates in the acute mobilization of circulating neutrophils to sites of tissue injury. Stored in the mobilized neutrophils, antimicrobial peptides and the bactericidal/ permeability-increasing protein (BPI) contribute to the elimination of bacteria (8, 9). BPI, another LBP, is a 55-kDa cationic protein specifically active against Gram-negative bacteria. It increases the permeability of the bacterial membranes (10). Accumulated extracellularly, BPI opsonizes bacteria, which enhances phagocytosis by neutrophils (11). LBP and BPI are structurally related, with 45% sequence identity. They have a coordinated function in the response to invading bacteria. The antibacterial BPI displays LPSneutralizing properties and suppresses LPS inflammatory activity whereas LBP is an acute-phase reactant (8, 12) that displays a concen...

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Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes

Cited by 161 publications

References 250 publications

Necrotizing enterocolitis: A multifactorial disease with no cure

Necrotizing enterocolitis: A multifactorial disease with no cure

Antimicrobial activity of potato aspartic proteases (StAPs) involves membrane permeabilization

Evidence of a bactericidal permeability increasing protein in an invertebrate, theCrassostrea gigas Cg-BPI

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