Effects of suramin on PMN interactions with different surfaces
G F Sud'ina1, M A Pushkareva, S I Galkina
1A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Abstract:
Human polymorphonuclear leukocytes (PMN) were found to tightly adhere on endothelial (lines EAhy926 and ECV304) and collagen surfaces under the influence of the chemotherapeutic drug suramin. This was observed by scanning electron microscopy and quantitated by myeloperoxidase assays. Suramin also inhibited Ca2+ ionophore A23187-stimulated leukotriene (LT) synthesis in PMN interaction with endothelial cells or with collagen surface. Suramin decreased the release of radiolabeled arachidonic acid (AA) and 5-lipoxygenase (5-LO) metabolites by prelabeled PMN stimulated with A23187. Using agents releasing the suramin-stimulated adhesion namely jasplakonolide and dextran sulfate, we observed a reversal of the suramin effect on leukotriene synthesis. Jasplakonolide released the adhesion of PMN on endothelial and collagen-coated surfaces and restored 5-LO activity. Dextran-sulfate released adhesion on collagen-coated surfaces and abolished suramin inhibition. Arachidonate could also overcome adhesion and inhibition of 5-LO. We conclude that suramin-induced tight attachment of PMN on to solid surfaces lead to decreased leukotriene synthesis during subsequent A23187 stimulation in the absence of exogenous substrates.
Insights
The chemotherapeutic drug suramin causes human white blood cells (polymorphonuclear leukocytes) to stick to surfaces, reducing the production of inflammatory leukotrienes. This adhesion and reduced leukotriene synthesis can be reversed by other agents.
Area of Science:
- Immunology
- Pharmacology
Background:
- Polymorphonuclear leukocytes (PMN) play a crucial role in inflammatory responses.
- Leukotriene synthesis is a key pathway in inflammation, involving enzymes like 5-lipoxygenase (5-LO).
Purpose of the Study:
- To investigate the effect of the chemotherapeutic drug suramin on PMN adhesion and leukotriene synthesis.
- To elucidate the mechanism by which suramin influences PMN-ECM interactions and inflammatory mediator production.
Main Methods:
- Scanning electron microscopy to visualize PMN adhesion.
- Myeloperoxidase assays to quantify PMN adherence.
- Measurement of leukotriene synthesis and arachidonic acid release.
- Utilizing agents like jasplakonolide and dextran sulfate to reverse suramin's effects.
Main Results:
- Suramin induced tight adhesion of PMN on endothelial cells and collagen surfaces.
- Suramin inhibited leukotriene (LT) synthesis stimulated by Ca2+ ionophore A23187.
- Suramin decreased the release of arachidonic acid (AA) and 5-lipoxygenase (5-LO) metabolites.
- Jasplakonolide and dextran sulfate reversed suramin-induced adhesion and restored LT synthesis.
- Arachidonate addition also overcame suramin's inhibitory effects.
Conclusions:
- Suramin-induced PMN adhesion to solid surfaces leads to decreased leukotriene synthesis.
- This effect is linked to the availability of substrates and the activity of the 5-LO pathway.
- Suramin's impact on PMN adhesion and function has implications for inflammatory processes.
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