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Respiratory Research
Published in: Respiratory Research 1/2006

Open Access 01-12-2006 | Research

Phenotypical and functional characterization of alveolar macrophage subpopulations in the lungs of NO2-exposed rats

Authors: Holger Garn, Anette Siese, Sabine Stumpf, Anka Wensing, Harald Renz, Diethard Gemsa

Published in: Respiratory Research | Issue 1/2006

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Abstract

Background

Alveolar macrophages (AM) are known to play an important role in the regulation of inflammatory reactions in the lung, e.g. during the development of chronic lung diseases. Exposure of rats to NO2 has recently been shown to induce a shift in the activation type of AM that is characterized by reduced TNF-α and increased IL-10 production. So far it is unclear, whether a functional shift in the already present AM population or the occurrence of a new, phenotypically different AM population is responsible for these observations.

Methods

AM from rat and mice were analyzed by flow cytometry for surface marker expression and in vivo staining with PKH26 was applied to characterize newly recruited macrophages. Following magnetic bead separation, AM subpopulations were further analyzed for cytokine, inducible NO synthase (iNOS) and matrix metalloproteinase (MMP) mRNA expression using quantitative RT-PCR. Following in vitro stimulation, cytokines were quantitated in the culture supernatants by ELISA.

Results

In untreated rats the majority of AM showed a low expression of the surface antigen ED7 (CD11b) and a high ED9 (CD172) expression (ED7-/ED9high). In contrast, NO2 exposure induced the occurrence of a subpopulation characterized by the marker combination ED7+/ED9low. Comparable changes were observed in mice and by in vivo labeling of resident AM using the dye PKH26 we could demonstrate that CD11b positive cells mainly comprise newly recruited AM. Subsequent functional analyses of separated AM subpopulations of the rat revealed that ED7+ cells showed an increased expression and production of the antiinflammatory cytokine IL-10 whereas TNF-α production was lower compared to ED7- AM. However, iNOS and IL-12 expression were also increased in the ED7+ subpopulation. In addition, these cells showed a significantly higher mRNA expression for the matrix metalloproteinases MMP-7, -8, -9, and -12.

Conclusion

NO2 exposure induces the infiltration of an AM subpopulation that, on the one hand may exert antiinflammatory functions by the production of high amounts of IL-10 but on the other hand may contribute to the pathology of NO2-induced lung damage by selective expression of certain matrix metalloproteinases.
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Metadata
Title
Phenotypical and functional characterization of alveolar macrophage subpopulations in the lungs of NO2-exposed rats
Authors
Holger Garn
Anette Siese
Sabine Stumpf
Anka Wensing
Harald Renz
Diethard Gemsa
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2006
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-7-4

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