NK1.1 + cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock

J Leukoc Biol. 2017 Jul;102(1):127-134. doi: 10.1189/jlb.3A0716-333R. Epub 2017 May 17.

Abstract

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1+ cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1+ cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1+ cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1+ cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut.

Keywords: T cell; cytokines; leukocytes; natural killer cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / immunology
  • Animals
  • Antigens, Ly / blood
  • Antigens, Ly / immunology*
  • Aspartate Aminotransferases / blood
  • Aspartate Aminotransferases / immunology
  • Cytokines / blood
  • Cytokines / immunology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily B / blood
  • NK Cell Lectin-Like Receptor Subfamily B / immunology*
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / immunology*
  • Shock, Hemorrhagic / pathology
  • Wounds and Injuries / blood
  • Wounds and Injuries / immunology*
  • Wounds and Injuries / pathology

Substances

  • Antigens, Ly
  • Cytokines
  • Klrb1c protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily B
  • Aspartate Aminotransferases
  • Alanine Transaminase