Class A scavenger receptor (CD204) attenuates hyperoxia-induced lung injury by reducing oxidative stress

J Pathol. 2007 May;212(1):38-46. doi: 10.1002/path.2150.

Abstract

To clarify the role of macrophage class A scavenger receptors (SR-A, CD204) in oxidative lung injury, we examined lung tissue of SR-A deficient (SR-A(-/-)) and wild-type (SR-A(+/+)) mice in response to hyperoxic treatment. Protein levels of bronchoalveolar lavage fluid (BALF) and pulmonary oedema (wet : dry weight ratios) were higher in SR-A(-/-) mice than those in SR-A(+/+) mice. Cumulative survival was significantly decreased in SR-A(-/-) mice. However, there were no differences in BALF macrophage and neutrophil count between the two groups. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that messenger RNA (mRNA) levels of the inducible nitric oxide synthase (iNOS) were increased during hyperoxic injury, and this increase was more prominent in SR-A(-/-) mice. Expression levels of iNOS in alveolar macrophages after hyperoxia in vivo and in vitro were higher in SR-A(-/-) macrophages compared with SR-A(+/+) macrophages. Immunohistochemistry using anti-nitrotyrosine antibodies revealed distinctive oxidative stress in the injured lung in both groups, but it was more remarkable in the SR-A(-/-) mice. After hyperoxic treatment, pulmonary mRNA levels of tumour necrosis factor-alpha(TNF-alpha) were elevated more rapidly in SR-A(-/-) mice than in SR-A(+/+) mice. Together these results suggest that SR-A expression attenuates hyperoxia-induced lung injury by reducing macrophage activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Hyperoxia / metabolism
  • Hyperoxia / pathology
  • Immunohistochemistry
  • Macrophage Activation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress
  • RNA, Messenger / analysis
  • Respiratory Distress Syndrome / metabolism*
  • Respiratory Distress Syndrome / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class A / metabolism*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Tyrosine / metabolism

Substances

  • RNA, Messenger
  • Scavenger Receptors, Class A
  • Tumor Necrosis Factor-alpha
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase Type II