Modulation of neutrophil function by lysozyme. Potential negative feedback system of inflammation.

Gordon, Leo I.; Douglas, Steven D.; Kay, Neil E.; Osserman, Elliott F.; Jacob, Harry S.

doi:10.1172/jci109443

Cited by 127 publications

(48 citation statements)

References 30 publications

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“…LYZ is an antimicrobial peptide secreted by activated monocytes that damages bacterial cell walls by catalyzing hydrolysis of peptidoglycan of Gram-positive bacteria. Like GPX2, it is elevated in inflamed tissue in response to infection, and it is thought to function in a negative-feedback system designed to antagonize the inflammatory response (22).…”

Section: Discussionmentioning

confidence: 99%

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

Jensen

Thymann

Cilieborg

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

103

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Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either antibiotics (oral and parenteral doses of gentamycin, ampicillin, and metronidazole, ANTI, n ϭ 11) or saline in the control group (CON, n ϭ 13), given twice daily. NEC lesions and intestinal structure, function, microbiology, and immunity markers were recorded. None of the ANTI but 85% of the CON pigs developed NEC lesions by day 5 (0/11 vs. 11/13, P Ͻ 0.05). ANTI pigs had higher intestinal villi (ϩ60%), digestive enzyme activities (ϩ53-73%), and goblet cell densities (ϩ110%) and lower myeloperoxidase (Ϫ51%) and colonic microbial density (10 5 vs. 10 10 colony-forming units, all P Ͻ 0.05). Microarray transcriptomics showed strong downregulation of genes related to inflammation and innate immune response to microbiota and marked upregulation of genes related to amino acid metabolism, in particular threonine, glucose transport systems, and cell cycle in 5-day-old ANTI pigs. In a follow-up experiment, 5 days of antibiotics prevented NEC at least until day 10. Neonatal prophylactic antibiotics effectively reduced gut bacterial load, prevented NEC, intestinal atrophy, dysfunction, and inflammation and enhanced expression of genes related to gut metabolism and immunity in preterm pigs.

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Section: Discussionmentioning

confidence: 99%

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

Jensen

Thymann

Cilieborg

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

103

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“…Lysozyme 2 (LYZ2) is a member of the lysozyme family which consists of enzymes that have an important role in the innate immune system by attacking invading bacteria (Gordon et al 1979). As the immune system has an important role in early embryonic development, the increased expression of LYZ2 in the R heifers could mean that the retarded embryo may have triggered an immune response.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of endometrial gene expression and metabolic parameters in beef heifers yielding viable or non-viable embryos on Day 7 after insemination

Beltman

Forde

Furney

et al. 2010

Reprod. Fertil. Dev.

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Abridged title: Endometrial gene expression and metabolic parameters in subfertile beef heifers. AbstractThe objective of this study was to compare the hormonal, metabolic characteristics and endometrial gene expression profiles in beef heifers yielding either a viable or a degenerate embryo on Day 7 after insemination as a means to explain differences in embryo survival.Oestrus was synchronised in cross bred beef heifers (n=145) using a CIDR-prostaglandin protocol and heifers (n=102) detected in standing oestrus (within 24-48 h post CIDR removal) were inseminated 12-18 h after detection of oestrus (Day 0) with frozen-thawed semen from a single ejaculate of a bull with proven fertility. Blood samples were collected from Day 4 to Day 7 post oestrus to measure progesterone (on Days 4, 5 and 7), insulin and IGF-I (on Days 4 and 6) and urea concentrations (on Day 7). All animals were slaughtered on Day 7. Uterine pH was also determined. Animals from which an embryo was recovered were classified as either having a viable embryo (morula/blastocyst stage); n=32, or a retarded embryo (arrested at 2-to 16-cell stage); n=19. The overall recovery rate was 64%. There was no significant difference in blood parameters measured or uterine pH at slaughter between the heifers with either a viable or retarded embryo. The relative abundance of 9 transcripts out of 53 tested from the endometrial tissue was different between heifers with a viable embryo or retarded embryo: MOGAT1, PFKB2, LYZ2, SVS8, UHRF1, PTGES, AGPAT4, DGKA and HGPD. Both LYZ2 and UHRF1 are associated with regulation of the immune system. PFKFB2 is a mediator in glycolysis and MOGAT, AGPAT4 and DGKA belong to the triglyceride synthesis pathway. PTGES and HGPD belong to the prostaglandin pathway.Both of these metabolic pathways are important for early embryonic development. In conclusion, retarded embryo development in this study was not related to serum progesterone, IGF-I, insulin or urea concentrations nor to uterine pH at slaughter. However, altered expression of genes involved in the prostaglandin and triglyceride pathways, as well as 2 genes that are closely associated with the regulation of immunity in the endometrium may indicate a uterine component to the retardation of the embryos in these beef heifers.

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“…51 Lysozyme can limit the migration of neutrophils into damaged tissue and might function as an anti-inflammatory agent. 54 To our knowledge this is the first report on the killing activity of milk protein components against the protozoan parasite E. histolytica. The only work concerning the effect of lysozyme and complement-dependent lysis of E. histolytica was reported 20 years ago.…”

Section: Amoebicidal Effect Of Human Milk Is Due To the Protein Fractmentioning

confidence: 92%

Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme

León-Sicairos¹,

López-Soto²,

Reyes-López³

et al. 2006

Clinical Medicine & Research

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Entamoeba histolytica is a pathogenic, parasitic protozoan that can infect the large intestine and cause amoebiasis, an illness responsible for at least 100,000 deaths annually worldwide. The capacity of human milk to kill amoebas 6,15 and the amoebicidal action of secretory immunoglobulin type A (sIgA) 16 have been reported. However, it is unknown which other components of milk are amoebicides. As milk contains several microbicidal components, we fractionated milk and tested each fraction against trophozoites in axenic cultures to describe any amoebicidal effects of other components of human and bovine milk such as lactoferrin, lysozyme and sIgA. We also sought to identify any combined effect among these molecules. Objectives: To identify amoebicidal components in human milk and the effect of iron on the amoebicidal activity. Original ResearchDesign: Investigation in axenic cultures of Entamoeba histolytica trophozoites.Methods: Amoebas were treated with 5%-20% of human, bovine and swine milk, with 10% of human milk fractions (i.e., casein, proteins except casein and fat) or with 1 mg/ml of human milk apo-lactoferrin, human secretory immunoglobulin type A (sIgA) and chicken egg-white lysozyme (i.e., purified proteins). Milk proteins were detected using immunoblot. Confocal microscopy was used to define the interaction of milk proteins (100 µM each) and amoebas. Experiments were done at least three times in triplicate, and mean and standard deviations were calculated.Results: Human and bovine milk were amoebicidal showing a concentration-dependent effect. The amoebicidal effect was increased in the absence of iron. Milk protein fractions, with the exception of casein, were the components responsible for the amoebicidal activity found. Apo-lactoferrin, sIgA and lysozyme were identified in the amoebicidal milk protein fraction. Apo-lactoferrin showed the major amoebicidal effect. These proteins, either alone or in combination, showed a killing effect on the trophozoites.They bound to the amoebic membrane causing cell rounding, lipid disruption and damage. Conclusions:Milk proteins such as apo-lactoferrin, sIgA and lysozyme are able to kill Entamoeba histolytica trophozoites.This study confirms the importance of feeding breast milk to newborns.

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Modulation of neutrophil function by lysozyme. Potential negative feedback system of inflammation.

Cited by 127 publications

References 30 publications

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

Characterisation of endometrial gene expression and metabolic parameters in beef heifers yielding viable or non-viable embryos on Day 7 after insemination

Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme

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