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Anti-inflammatory drugs modulate histamine release from mast cells induced by fibrinogen degradation products
E Wojtecka-Lukasik1, J Stachurska, M Kopeć
1Department of Biochemistry, Institute of Rheumatology, Warsaw, Poland.
Abstract:
The products resulting from proteolytic degradation of human fibrinogen (FDP) were found to induce the release of histamine from rat peritoneal mast cells. Low molecular weight, dialysable peptides (FDP) showed the highest dose dependent, histamine releasing activity. Histamine release induced by FDP was effectively inhibited by the gold compound auranofin at a concentration of 10(-5)-10(-7) mol/l and also by the non-steroidal anti-inflammatory drugs BW 755c, timegadine, medosan, naproxen, and aspirin at the higher concentration range of 10(-4)-10(-6) mol/l. It is concluded that the release of histamine from mast cells may be modulated to some extent by anti-inflammatory drugs, especially auranofin, BW 755c and timegadine, a functional property which may be beneficial in the management of joint disease.
Insights
Fibrinogen degradation products (FDP) release histamine from mast cells. Anti-inflammatory drugs, particularly auranofin and BW 755c, can inhibit this release, potentially aiding joint disease management.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Fibrinogen is a key protein in blood coagulation.
- Proteolytic degradation of fibrinogen yields fragments known as FDP.
- Mast cells are crucial immune cells involved in allergic reactions and inflammation.
Purpose of the Study:
- To investigate the histamine-releasing activity of fibrinogen degradation products (FDP).
- To evaluate the inhibitory effects of anti-inflammatory drugs on FDP-induced histamine release.
- To explore the potential therapeutic implications for joint diseases.
Main Methods:
- Incubation of rat peritoneal mast cells with FDP.
- Measurement of histamine release.
- Assessment of inhibition by auranofin and various non-steroidal anti-inflammatory drugs (NSAIDs).
Main Results:
- FDP induced dose-dependent histamine release from mast cells.
- Low molecular weight, dialysable FDP exhibited the highest activity.
- Auranofin significantly inhibited histamine release at 10(-5)-10(-7) mol/l.
- NSAIDs (BW 755c, timegadine, medosan, naproxen, aspirin) inhibited release at 10(-4)-10(-6) mol/l.
Conclusions:
- Fibrinogen degradation products stimulate histamine release from mast cells.
- Anti-inflammatory drugs, notably auranofin, BW 755c, and timegadine, can modulate this histamine release.
- This modulation suggests a potential benefit of these drugs in managing inflammatory joint diseases.