Modulation of the effects of alveolar macrophages on lung fibroblast collagen production rate

Journal Article · Thu Jan 01 04:00:00 EST 1987 · Am. Rev. Respir. Dis.; (United States)

OSTI ID:6803055

Clark, J G; Greenberg, J

Alveolar macrophages (AM) may function as effector cells that can either stimulate or inhibit lung fibroblast collagen production. However, conditions that determine the predominant effect of AM on fibroblasts are not well understood. To delineate factors that modulate the effects of AM on lung fibroblasts, we studied the interaction of AM products and fibroblasts in vitro. The AM were obtained by bronchoalveolar lavage of hamsters with bleomycin-induced pulmonary fibrosis. Conditioned medium (CM) from the AM cultures was incubated in varying amounts with lung fibroblast (IMR-90) cultures. After metabolic labeling with (/sup 3/H)proline, fibroblast collagen production based on procollagen-specific radioactivity was determined. Macrophage CM in concentrations greater than 5% suppressed collagen production, an event attributed to the macrophage-derived suppressive factor that we have previously characterized. Macrophages were also determined to produce PGE2 in culture. Authentic PGE2 at concentrations found in CM was found to suppress fibroblast collagen production, indicating that AM-derived PGE2 contributes to the suppressive activity in CM. To examine possible stimulatory factors in CM, the fibroblasts were preincubated with indomethacin. This approach was based on our previous observation that AM-derived suppressive factor increases endogenous fibroblast PGE2 and that its activity can be blocked by indomethacin. Macrophage CM in a concentration of 20% did not suppress the collagen production of indomethacin-treated fibroblasts. However, CM concentrations of 5 and 10% increased collagen production (173 and 143% of control values, respectively), indicating the presence of stimulatory factor(s) in macrophage-conditioned medium.

• Research Organization: Washington Univ., St. Louis, MO
• OSTI ID: 6803055
• Journal Information: Am. Rev. Respir. Dis.; (United States), Journal Name: Am. Rev. Respir. Dis.; (United States) Vol. 1; ISSN ARDSB
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AZOLES
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
BODY
CARBOXYLIC ACIDS
COLLAGEN
CONNECTIVE TISSUE CELLS
FIBROBLASTS
FIBROSIS
FUNCTIONS
HAMSTERS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
HYDROXYPROLINE
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LAVAGE
LUNGS
MACROPHAGES
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHAGOCYTES
PROLINE
PROSTAGLANDINS
PROTEINS
PYRROLES
PYRROLIDINES
RESPIRATORY SYSTEM
RODENTS
SCLEROPROTEINS
SOMATIC CELLS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES