Enhanced macrophage-fibroblast interactions in the pulmonary interstitium increases fibrosis after silica injection to monocyte-depleted mice
The role of interstitial vs. alveolar macrophages in the generation of pulmonary fibrosis after silica was examined. Using whole body irradiation to delay the inflammatory response and so retard particulate clearance, many more instilled silica particles reached the interstitial macrophages in the first 2 weeks than after silica alone. This was followed by greatly increased fibroblast proliferation and deposition of collagen in the irradiation plus silica group, which developed large interstitial granulomas at the sites of silica retention. Although alveolar macrophages containing silica were seen in both silica groups, more interstitial particles were observed after combined irradiation and silica, significantly more silica was recovered in a residue from the lungs at 16 weeks, and pulmonary fibrosis at 8-16 weeks was greater than in all other groups. The results indicate that increased fibroblast growth and collagen synthesis in vivo are associated with phagocytosis of silica by interstitial macrophages rather than by free alveolar macrophages. It is suggested that transfer of a macrophages-derived growth factor to fibroblasts is more efficient when it occurs within the pulmonary interstitium.
- Research Organization:
- Univ. of Manitoba, Winnipeg (Canada)
- OSTI ID:
- 6212011
- Journal Information:
- Am. J. Pathol.; (United States), Vol. 134:2
- Country of Publication:
- United States
- Language:
- English
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FIBROBLASTS
CELL PROLIFERATION
LUNGS
FIBROSIS
MACROPHAGES
SILICA
LUNG CLEARANCE
COLLAGEN
GRANULOMAS
GROWTH FACTORS
HYDROXYPROLINE
MICE
PHAGOCYTOSIS
WHOLE-BODY IRRADIATION
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AZOLES
BODY
CARBOXYLIC ACIDS
CHALCOGENIDES
CLEARANCE
CONNECTIVE TISSUE CELLS
DISEASES
EXCRETION
EXTERNAL IRRADIATION
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
IRRADIATION
MAMMALS
MINERALS
MITOGENS
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDE MINERALS
OXIDES
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PHAGOCYTES
PROTEINS
PYRROLES
PYRROLIDINES
RESPIRATORY SYSTEM
RODENTS
SCLEROPROTEINS
SILICON COMPOUNDS
SILICON OXIDES
SOMATIC CELLS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals