Macrophage/fibroblast coculture induces macrophage inflammatory protein-1alpha production mediated by intercellular adhesion molecule-1 and oxygen radicals.
This study examined the cell-to-cell interaction between fibroblasts and macrophages as a possible contributor to the chronic inflammatory state. In a coculture system, consisting of macrophages layered over confluent fibroblasts, there was a significant increase in macrophage inflammatory protein 1alpha (MIP-1alpha) compared with control cultures. ICAM-1 adhesion was identified as an important stimulus of MIP-1alpha production by using ICAM-1-specific monoclonal antibodies. Furthermore, fibroblasts from ICAM-1 knockout mice induced significantly less MIP-1alpha production from peritoneal macrophages when compared to control fibroblasts. In addition, it appeared that oxygen radicals functioned as activating molecules during cellular interaction and production of MIP-1alpha, as the addition of the antioxidant N-acetylcysteine (NAC) prevented MIP-1alpha secretion. Thus, the ICAM-1 and oxygen radical-mediated induction of MIP-1alpha associated with a macrophage/fibroblast coculture system provides one possible mechanism by which immune/inflammatory cell interactions may augment chemokine production and exacerbate chronic inflammatory diseases.
Steinhauser
M L
ML
University of Michigan Medical School, Department of Pathology, Ann Arbor 48109-0602, USA. matthewl@umich.edu
Kunkel
S L
SL
Hogaboam
C M
CM
Evanoff
H
H
Strieter
R M
RM
Lukacs
N W
NW
D000818:Animals; D002450:Cell Communication; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005355:Fibrosis; D005609:Free Radicals; D005786:Gene Expression Regulation; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D017154:Stromal Cells / Q000502:physiology
D016207:Cytokines; D005609:Free Radicals; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1