Role of reactive nitrogen species in development of hepatic injury in a C57BL/6 mouse model of human granulocytic anaplasmosis

Michelle D. Browning, Justin W. Garyu, J. Stephen Dumler, Diana G. Scorpio

Research output: Contribution to journalArticle

Abstract

Human granulocytic anaplasmosis (HGA), caused by the granulocytic rickettsia-like organism Anaplasma phagocytophilum, is the 3rd most frequent vector-borne infection in North America. To understand the disease mechanisms of HGA, we developed a murine model that lacks clinical disease yet exhibits characteristic histopathologic and immunologic changes. Because the degree of hepatic histopathology is unrelated to high bacterial numbers, tissue injury in HGA is thought to occur due to products of innate immunity, such as nitric oxide (NO) and reactive nitrogen species (RNS) from cytokine-activated macrophages. To test the hypothesis that RNS cause hepatic tissue damage, mice received either water treated with a nonspecific inhibitor of inducible nitric oxide synthase, L-NAME, or untreated water for 7 to 10 d before infection and continuing thereafter. Mice were euthanized for tissue harvest at 0, 7,14, or 21 d after infection to assess differences in histopathology, hepatic bacterial load, RNS quantity in urine and liver, and serum chemistry values. Overall, L-NAME treatment had a beneficial effect, resulting in lower histopathology scores and RNS levels compared with those of untreated mice. There were no significant differences in hepatic bacterial load among treatment groups of infected mice. The observed increases in serum glucose and alanine aminotransferase levels on day 14 appear to be unexpected side effects of L-NAME administration. HGA is best characterized as an immunopathologic disease rather than one caused by direct bacterial injury to the host. Therefore, human and animal patients with HGA likely would benefit from therapy targeting reduced inflammation to supplement anti-infective modalities.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalComparative Medicine
Volume56
Issue number1
StatePublished - Feb 2006

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Anaplasmosis
Reactive Nitrogen Species
anaplasmosis
Inbred C57BL Mouse
NG-Nitroarginine Methyl Ester
animal models
liver
histopathology
Liver
Wounds and Injuries
nitrogen
Tissue
mice
Bacterial Load
rickettsia-like organisms
Water
Macrophages
Nitric Oxide Synthase Type II
vector-borne diseases
Infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Role of reactive nitrogen species in development of hepatic injury in a C57BL/6 mouse model of human granulocytic anaplasmosis. / Browning, Michelle D.; Garyu, Justin W.; Dumler, J. Stephen; Scorpio, Diana G.

In: Comparative Medicine, Vol. 56, No. 1, 02.2006, p. 55-62.

Research output: Contribution to journalArticle

Browning, Michelle D. ; Garyu, Justin W. ; Dumler, J. Stephen ; Scorpio, Diana G. / Role of reactive nitrogen species in development of hepatic injury in a C57BL/6 mouse model of human granulocytic anaplasmosis. In: Comparative Medicine. 2006 ; Vol. 56, No. 1. pp. 55-62.
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