| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology and
* Division of Pediatric Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
1Correspondence: Biophysics 203, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA. E-mail: rreeves{at}welch.jhu.edu
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.—Matesic, L. E., Niemitz, E. L., De Maio, A., Reeves, R. H. Quantitative trait loci modulate neutrophil infiltration in the liver during LPS-induced inflammation.
Key Words: mapping • quantitative trait loci • inbred strains (A/J and C57BL/6J) • sepsis • multiple organ dysfunction syndrome
This article has been cited by other articles:
|
|
 |
|
  I. V. Yang, C. M. Wade, H. M. Kang, S. Alper, H. Rutledge, B. Lackford, E. Eskin, M. J. Daly, and D. A. Schwartz Identification of Novel Genes That Mediate Innate Immunity Using Inbred Mice Genetics, December 1, 2009; 183(4): 1535 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Laragione, N. C. Yarlett, M. Brenner, A. Mello, B. Sherry, E. J. Miller, C. N. Metz, and P. S. Gulko The Arthritis Severity Quantitative Trait Loci Cia4 and Cia6 Regulate Neutrophil Migration into Inflammatory Sites and Levels of TNF-{alpha} and Nitric Oxide J. Immunol., February 15, 2007; 178(4): 2344 - 2351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Fulton, R. H. Reeves, M. Takeya, and A. De Maio A Quantitative Trait Loci Analysis to Map Genes Involved in Lipopolysaccharide-Induced Inflammatory Response: Identification of Macrophage Scavenger Receptor 1 as a Candidate Gene J. Immunol., March 15, 2006; 176(6): 3767 - 3773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. I. Rutitzky, H. J. Hernandez, Y.-S. Yim, D. E. Ricklan, E. Finger, C. Mohan, I. Peter, E. K. Wakeland, and M. J. Stadecker Enhanced Egg-Induced Immunopathology Correlates With High IFN-{gamma} in Murine Schistosomiasis: Identification of Two Epistatic Genetic Intervals J. Immunol., January 1, 2005; 174(1): 435 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Del Pozzo, D. Mascolo, A. Prisco, P. Barba, A. Anzisi, and J. Guardiola Lack of patent liver autoimmunity after breakage of tolerance in a mouse model Int. Immunol., October 1, 2003; 15(10): 1173 - 1181. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
