Lactoferrin protects neonatal rats from gut-related systemic infection

Edde, Lynn; Hipolito, Ronaldo B.; Hwang, F; Headon, Denis R.; Shalwitz, Robert A.; Sherman, Michael P.

doi:10.1152/ajpgi.2001.281.5.g1140

Cited by 121 publications

(91 citation statements)

References 76 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lactoferrin is an integral part of the innate immune system [30] which is recognized as an immunomodulator of leukocyte populations, including neutrophils [32], peritoneal macrophages [14], natural killer cells [11,41], T cells [12], and B cells [51]. More importantly, Lactoferrin as an adjuvant is capable of enhancing the T cell mediated DTH response to a variety of antigens including Mycobacterium bovis Calmette Guerin (BCG) [27,49,50].…”

Section: Discussionmentioning

confidence: 99%

“…Lactoferrin is an integral part of the innate immune system [30], with immunomodulatory activities on leukocytes to increase phagocytic activity of neutrophils e-mail: Jeffrey.K.Actor@uth.tmc.edu. [32], enhance activation of peritoneal macrophages [14], increase natural killer cell activity [11,41], and promote maturation of T cells [12] and B cells [51]. Furthermore, Lactoferrin is capable of enhancing delayed type hypersensitivity (DTH) responses, as measured by foot pad swelling, to a variety of antigens, including sheep red blood cells (SRBC), ovalbumin (OVA), and Mycobacterium bovis Calmette Guerin (BCG) [8,49,50].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

Hwang¹,

Wilk²,

Bangale³

et al. 2007

Med Microbiol Immunol

View full text Add to dashboard Cite

Lactoferrin possesses a wide range of immunomodulatory activities, including promotion of the delayed type hypersensitivity response (DTH) towards BCG (Bacillus Calmette Guerin) antigens. Addition of Lactoferrin as an adjuvant to the BCG vaccine was previously demonstrated to augment protection against subsequent mycobacterial challenge, with concomitant development of a strong T cell helper type 1 (T H 1) immunity. Because generation of T H 1 immunity is in large part dependent on the balance of monocytic pro-and anti-inflammatory cytokines, the effect of Lactoferrin on leukocytes was investigated. Lactoferrin enhanced proinflammatory responses in a dose-dependant manner from splenocyte and adherent (F4/80 + ) splenocyte populations, bone marrow derived monocytes (BMM), and J774A.1 cultured cells. In all scenarios tested, Lactoferrin induced a strong increase in the ratio of IL-12:IL-10 production from LPS stimulated cells. Examination of Lactoferrin effects on BCG infected J774A.1 cells and on BMM revealed similar immunomodulatory effects, with particularly strong increase in IL-12 production. Furthermore, immunization of mice with BCG admixed with Lactoferrin led to increased generation of CD4+ cells expressing IFN-γ upon restimulation with BCG antigens. These results provide molecular evidence to support the role of Lactoferrin as an adjuvant candidate to augment development of DTH response to vaccine antigens.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

Hwang¹,

Wilk²,

Bangale³

et al. 2007

Med Microbiol Immunol

View full text Add to dashboard Cite

show abstract

“…E. coli strain Ec5 was used to induce enteral infection because it is an isolate from a human preterm infant and has the following surface determinants associated with virulence, O18: K1:H7 (9). This strain has been used in past reports of enteral infection in neonatal rats and was prepared as described in those studies (6,18).…”

mentioning

confidence: 99%

Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine

et al. 2005

Self Cite

View full text Add to dashboard Cite

Antimicrobial proteins and peptides are key effectors of innate immunity at mucosal surfaces in adult animals (21), but their role in host defense during perinatal intestinal development is not clearly delineated. Paneth cells are specialized epithelia in the crypts of the small bowel that control the intestinal growth of bacterial pathogens through the secretion of antimicrobial proteins and peptides (11). Paneth cells secrete their antimicrobial-rich granules upon exposure to pathogenic bacteria and bacterial products (1,11,12), and alphadefensins account for 70% of the secreted bactericidal activity of Paneth cells (1).Neonatal necrotizing enterocolitis is a disease mainly of preterm human infants, but its pathogenesis is incompletely understood (8). It is hypothesized that abnormal bacterial colonization of the small bowel plays a role (3). A causative association between Paneth cells and necrotizing enterocolitis has been proposed because preterm infants inadequately express alpha-defensins in the small bowel (10). Additionally, Paneth cells in surgical specimens from human infants with necrotizing enterocolitis have a deficiency in lysozyme (4), a prominent antimicrobial protein in Paneth cell granules (11). The inability of neonatal Paneth cells to control the growth of bacterial pathogens in the lumen of the small bowel is an attractive hypothesis related to the initiation of necrotizing enterocolitis, but there is no in vivo evidence that Paneth cells provide host defense in the neonatal small bowel.This investigation postulated that ablating Paneth cells in neonatal rats would reduce the ability of the neonatal small bowel to clear an infection caused by enteroinvasive Escherichia coli. To test this hypothesis, dithizone was given systemically to neonatal rats. Since dithizone selectively destroys Paneth cells in adult rats (16), we quantified the effects of dithizone on the Paneth cells of neonatal rats. After dithizone treatment, newborn rats were infected with an intragastric dose of Escherichia coli, and the quantitative clearance of this bacterium from the small bowel lumen was measured.Effect of dithizone on Paneth cells in the noninfected neonatal small bowel. For studies that examined the effects of dithizone, specific-pathogen-free Sprague Dawley rats (Harlan, San Diego, CA) were studied between 4 and 5 days of age. The studies described below were approved by the Animal Use Committee of the University of California, Davis.Dithizone (Sigma-Aldrich, St. Louis, MO) was suspended in 25 mM Li 2 CO 3 buffer, stirred for 2 h at 37°C, and then filtered through preweighed Whatman 1 paper (Whatman Inc., Clifton, NJ). The filter paper was completely dried after filtration and was reweighed to determine the mg/ml of dissolved dithizone. The measurement of dissolved dithizone was used to properly dose administration of the dye.Three separate litters of 4-day-old pups were given an intraperitoneal (i.p.) injection of either filter-sterilized dithizone (75 mg/kg of body weight) in mM Li 2 CO 3 buffer, 25 mM...

show abstract

“…LF and LFcin are effective against bacteria, fungi, and viruses (Table 3, Figure 1) [3]. In mouse experiments, oral administration of bovine LF reduced the number of bacterial infections in the gastrointestinal tract [23], while promoting the growth of bacteria with low iron requirements such as Lactobacillus and Bifidobacterium, which are generally believed to be beneficial to the host [24,25]. Oral LF was also found to be effective against experimentally induced Urinary tract infection (UTI) and endotoxin-induced septic shock [26,27].…”

Section: Function and Spectrummentioning

confidence: 99%

Lactoferrin and Its Role in Neonatology: A Review Article

Sharma¹

2015

JPNC

View full text Add to dashboard Cite

Lactoferrin (LF) is a glycoprotein, which is present in milk of mammals. It has been proven to plays a very important role in innate immune host defences. It is well known that Neonatal sepsis and necrotizing enterocolitis (NEC) are responsible for significant morbidity and mortality in the new-born, especially in VLBW (1500 grams at birth) infants. The ill effects of sepsis and NEC persist in spite of appropriate and effective antibiotic therapy and have been associated with poor long term outcome. In the few recent trials which have been conducted around the globe, in field of neonatology, role of LF in prevention of neonatal sepsis and NEC has been strengthened. Furthermore many trials are underway and only future may provide a definite answer of LF role in sepsis and NEC. This review article has been written to through some light on the recent work that has already been done, to strengthen the role of LF in neonatal sepsis and the work that is still under process.

show abstract

Lactoferrin protects neonatal rats from gut-related systemic infection

Cited by 121 publications

References 76 publications

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine

Lactoferrin and Its Role in Neonatology: A Review Article

Contact Info

Product

Resources

About