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Platelet activation by polymorphonuclear leukocytes exposed to chemotactic agents
A Del Maschio1, V Evangelista, G Rajtar
1Istituto di Ricerche Farmacologiche Mario Negri, Giulio Bizzozero Laboratory of Platelet and Leucocyte Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
The American Journal of Physiology
|March 1, 1990
Summary
Stimulated leukocytes activate human platelets, increasing aggregation and calcium signaling. This platelet-leukocyte interaction, mediated by soluble factors and cell contact, has significant implications for cardiovascular health and drug development.
Area of Science:
- Hematology
- Immunology
- Biochemistry
Background:
- Human platelets play a crucial role in hemostasis and inflammation.
- Leukocyte activation can influence platelet function, but the underlying mechanisms require further elucidation.
Purpose of the Study:
- To investigate the impact of polymorphonuclear leukocytes (leukocytes) on human platelet aggregation and intracellular calcium (Ca2+) mobilization.
- To explore the role of chemotactic stimuli and cell-cell interactions in platelet-leukocyte cross-talk.
Main Methods:
- Human platelets loaded with aequorin were analyzed using a platelet-ionized calcium aggregometer.
- Simultaneous measurement of platelet aggregation and intraplatelet Ca2+ levels in the presence and absence of leukocytes.
- Leukocytes were stimulated with platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (FMLP), or leukotriene B4 (LTB4).
Main Results:
- Platelets alone aggregated and mobilized Ca2+ only upon PAF stimulation.
- Leukocytes amplified PAF-induced platelet aggregation and Ca2+ mobilization.
- Leukocytes stimulated by FMLP or LTB4 also induced platelet aggregation and Ca2+ mobilization, with effects increasing with stimulus concentration and leukocyte number.
- Platelet thromboxane B2 production was significantly enhanced in the presence of leukocytes.
- Cell-free supernatants from stimulated leukocytes induced platelet activation, suggesting the release of soluble mediators.
Conclusions:
- Stimulated leukocytes release soluble factors that activate platelets, contributing to platelet aggregation and Ca2+ signaling.
- Both soluble mediators and direct cell-to-cell contact between platelets and leukocytes play a role in platelet activation.
- Platelet-leukocyte interactions have potential physiopathological relevance and offer a novel model for evaluating anti-platelet drugs.