Binding of leukotriene C/sub 4/ to rat lung fibroblasts and stimulation of collagen synthesis in vitro
Although prostaglandins of the E series, which are products of the cyclooxygenase pathway, have been known as inhibitors or down-regulators of fibroblasts proliferation and collagen synthesis, the more recently discovered products of the 5-lipoxygenase pathway have not been as extensively investigated with regard to fibroblast function. In this study, a sulfidopeptide product of the lipoxygenase pathway, leukotriene C/sub 4/ (LTC/sub 4/), was examined for its ability to modulate rat lung fibroblasts collagen synthesis and proliferation in vitro. The data revealed the ability of LTC/sub 4/ and to a lesser extent leukotriene D/sub 4/ (LTD/sub 4/) to stimulate collagen synthesis in a dose-dependent manner with affecting cellular proliferation as determined by radiolabeled thymidine incorporation; 1 nM LTC/sub 4/ caused an 85% increase above untreated controls in (/sup 3/H)proline incorporation into collagenous protein in the media, which was blocked by the putative leukotriene receptor antagonist FPL55712 (10 ..mu..M) and inhibited by cycloheximide and actinomycin D. Binding of (/sup 3/H(LTC/sub 4/ to these cells was specific, reversible, and saturable. Under equilibrium conditions, there was an estimated 2.39 x 10/sup 4/ receptors per cell. This binding was also inhibited by 10 ..mu..M FPL55712. Competitive binding studies show specificity of this binding for LTC/sub 4/ relative to LTD/sub 4/ and FPL55712. Furthermore, no significant conversion of LTC/sub 4/ to LTD/sub 4/ or leukotriene E/sub 4/ was noted during the binding studies. These results indicate the presence of specific LTC/sub 4/ receptors on these cells which may mediate the cellular effects on protein and collagen synthesis.
- Research Organization:
- Univ. of Michigan, Ann Arbor (USA)
- OSTI ID:
- 7142873
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:8; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
AZOLES
BIOSYNTHESIS
BODY
CARBOXYLIC ACIDS
CELL PROLIFERATION
COLLAGEN
CONFIGURATION INTERACTION
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHORESIS
FIBROBLASTS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
IN VITRO
LABELLED COMPOUNDS
LUNGS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROLINE
PROSTAGLANDINS
PROTEINS
PYRROLES
PYRROLIDINES
RATS
RESPIRATORY SYSTEM
RODENTS
SCLEROPROTEINS
SOMATIC CELLS
SYNTHESIS
TRITIUM COMPOUNDS
VERTEBRATES