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Updated: Jul 26, 2026
A Method for Generating Pulmonary Neutrophilia Using Aerosolized Lipopolysaccharide
Published on: December 15, 2014
Quantitative trait loci modulate neutrophil infiltration in the liver during LPS-induced inflammation
L E Matesic1, E L Niemitz, A De Maio
1Department of Physiology, Division of Pediatric Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Abstract:
A crucial aspect of the inflammatory response is the recruitment of activated neutrophils (PMN) to the site of damage. Lytic enzymes and oxygen radicals released by PMN are important in clearing an infection or cellular debris, but can also produce host tissue damage. Failure to properly regulate the inflammatory response contributes to a variety of human diseases like sepsis and multiple organ dysfunction syndrome, the leading cause of morbidity and mortality in surgical intensive care units. Many aspects of human disease pathology, including hepatic PMN infiltration, can be recapitulated in mice using an endotoxic shock model. Six quantitative trait loci that predispose to high infiltration of PMN in hepatic sinusoids after high-dose endotoxin administration were provisionally identified. Two of these loci, Hpi1 and Hpi2 on mouse chromosomes 5 and 13, were mapped to the significant and highly significant level using a low-resolution genome scan on 122 intercross animals. These loci interact epistatically to produce a high degree of PMN infiltration. Intercross and recombinant inbred strain mice with a specific genotype at these loci always had a high infiltration response, indicating that genotype analysis at just these two loci can accurately predict a high PMN infiltration response. Genetic predisposition to the degree of PMN infiltration in the inflammatory response in mice suggests that analogous genetic mechanisms occur in human beings that could be used for diagnostic purposes.
Insights
Researchers identified two key genetic loci, Hpi1 and Hpi2, that significantly influence neutrophil infiltration in mice. This finding suggests a genetic basis for inflammatory responses, potentially aiding in human disease diagnostics.
Area of Science:
- Immunology
- Genetics
- Inflammation Research
Background:
- Neutrophil (PMN) recruitment is vital for inflammatory responses but can cause host tissue damage.
- Dysregulated inflammation contributes to severe conditions like sepsis and multiple organ dysfunction syndrome.
- Hepatic PMN infiltration in mice models endotoxic shock, relevant to human diseases.
Purpose of the Study:
- To identify genetic factors controlling hepatic neutrophil infiltration in an endotoxic shock mouse model.
- To investigate the genetic predisposition to inflammatory responses.
Main Methods:
- A low-resolution genome scan was performed on 122 intercross mice.
- Quantitative trait loci (QTL) analysis was used to identify genetic loci associated with PMN infiltration.
- Epistatic interactions between identified loci were analyzed.
Main Results:
- Six quantitative trait loci predisposing to high PMN infiltration were provisionally identified.
- Two loci, Hpi1 and Hpi2, were mapped to significant and highly significant levels.
- Hpi1 and Hpi2 interact epistatically, accurately predicting high PMN infiltration based on genotype.
Conclusions:
- Genetic predisposition plays a significant role in regulating PMN infiltration during inflammation.
- The identified loci (Hpi1 and Hpi2) can predict inflammatory response severity.
- These findings suggest analogous genetic mechanisms in humans, offering potential for diagnostic applications.
