Effect of CCL2 antisense oligodeoxynucleotides on bacterial translocation and subsequent sepsis in severely burned mice orally infected with Enterococcus faecalis.
Summary of "Effect of CCL2 antisense oligodeoxynucleotides on bacterial translocation and subsequent sepsis in severely burned mice orally infected with Enterococcus faecalis."
Severely burned mice are susceptible to sepsis stemming from Enterococcus faecalis translocation due to the impaired generation of M1 macrophages (MÏ•) in local translocation sites. In our previous studies, CCL2 has been characterized as a major effector molecule on the burn-associated generation of M2MÏ•, an inhibitor cell for resident MÏ• conversion to M1MÏ•. In this study, we tried to protect burned mice orally infected with E. faecalis utilizing CCL2 antisense oligodeoxynucleotides (ODNs). We show that M2MÏ• in mesenteric lymph nodes (MLNs) were not demonstrated in burned mice treated with CCL2 antisense ODN. M1MÏ• were not induced by heat-killed E. faecalis from resident MÏ• transwell-cultured with MLN-MÏ• from burned mice, while M1MÏ• were induced by the same antigen from resident MÏ• transwell-cultured with MÏ• which were isolated from burned mice treated with CCL2 antisense ODN. Bacterial growth in MLNs was shown in burned mice orally infected with a lethal dose of E. faecalis. However, after the same infection, sepsis did not develop in burned mice treated with CCL2 antisense ODN. These results indicate that bacterial translocation and subsequent sepsis are controlled in burned mice orally infected with a lethal dose of E. faecalis by gene therapy utilizing CCL2 antisense ODN.
Affiliation
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX, USA.
Journal Details
This article was published in the following journal.
Name: European journal of immunology
ISSN: 1521-4141
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22002847
- DOI: http://dx.doi.org/10.1002/eji.201141572
Medical and Biotech [MESH] Definitions
Bacterial Translocation
The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis.
Rna, Antisense
RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. Endogenous antisense RNAs function as regulators of gene expression by a variety of mechanisms. Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes.
Dna, Antisense
DNA that is complementary to the sense strand. (The sense strand has the same sequence as the mRNA transcript. The antisense strand is the template for mRNA synthesis.) Synthetic antisense DNAs are used to hybridize to complementary sequences in target RNAs or DNAs to effect the functioning of specific genes for investigative or therapeutic purposes.
Sepsis
Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.
Receptors, Ccr2
CCR receptors with specificity for CHEMOKINE CCL2 and several other CCL2-related chemokines. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; BASOPHILS; and NK CELLS.
PubMed Articles
New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention.
Bacterial translocation from the gastrointestinal tract is an important pathway initiating late-onset sepsis and necrotizing enterocolitis in very low-birth-weight infants. The emerging intestinal mic...
Having previously observed that noradrenaline activation of β adrenergic receptors induces the synthesis of the chemokine monocyte chemoattractant protein (CCL2/MCP-1) in astrocytes, it is our intere...
BACKGROUND: Bacterial translocation is considered a major cause of initiation and development of systemic sepsis and multiple organ dysfunction in clinic. The aim of this study was to determine the ab...
ABSTRACT: BACKGROUND: : Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newb...
Antisense oligonucleotides are promising therapeutic agents against a variety of diseases. Effective delivery of these molecules is critical in view of their clinical application. Despite the richness...
Clinical Trials
Role of CCL2 in Alcoholic Liver Diseases
Immune dysregulations, including cytokines and chemokines secretions occurs in alcoholic liver disease. Serum levels and liver expression of CCL2 are increased in patients with alcoholic h...
Lactobacillus Plantarum 299v in Colon Surgery
Intestinal pathogenes are often involved in postoperative complications after colon surgery. Probiotic bacteria, i e live bacteria which have beneficial effects on the host when ingested,...
Cirrhotic patients are predisposed to bacterial infection. A large proportion of which is spontaneous bacterial peritonitis(SBP), which are mainly caused by enteric bacteria.SBP in a cirr...
The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure an...
The Study of Drotrecogin Alfa (Activated) in a Subpopulation of Adult Patients With Severe Sepsis
Severe sepsis is defined as a systemic inflammatory response syndrome that results from infection and is associated with acute organ dysfunction. It usually results from bacterial infectio...
