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[Analysis of platelet-derived factors that modulate functions of polymorphonuclear leukocytes]
Abstract:
Interactions between platelets and polymorphonuclear leukocytes (PMN) modulate their functions and play a role in the development of pathogenesis of some disease. Platelets secret various kinds of factors that affect PMN functions. They seemed to have important role in vivo, but little has been elucidated on exact mechanism of action and physiological meaning of each factor in relation to PMN functions. We studied the effects of platelets and released substances from activated platelets on the functions of PMN. Results were as follows. 1) Platelets enhanced bactericidal activities of PMN against E.coli. 2) Platelets had effects on the generation of superoxide anion (O2-) of PMN. Their effects were quite different according to the assay condition of PMN, that is, platelets inhibited O2- generation when PMN were at rest or stimulated slightly and they enhanced O2-generation of PMN that were stimulated with optimal condition. 3) Thrombin-activated platelets and their supernatant elicited a transient elevation of [Ca2] of PMN. The activity of the supernatant decreased by treating with hexokinase that decomposed ATP. Further treatment with trypsin abolished its activity almost completely. Considering with our additional experiments, factors that induced [Ca2+] elevation of PMN were ATP, beta-thromboglobulin and some trypsin-sensitive factor(s). 4) Supernatant of thrombin-activated platelets decreased random migration and chemokinesis of PMN.
Insights
Platelet interactions with polymorphonuclear leukocytes (PMN) impact immune responses. Activated platelets influence PMN bactericidal activity, superoxide generation, and migration, revealing key mechanisms in disease pathogenesis.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Context:
- Platelet-leukocyte interactions are crucial in inflammation and disease.
- The precise mechanisms by which platelets influence polymorphonuclear leukocyte (PMN) functions are not fully understood.
- Platelets release various factors that modulate PMN activity.
Purpose:
- To investigate the effects of platelets and substances released from activated platelets on PMN functions.
- To elucidate the role of platelet-derived factors in PMN bactericidal activity, superoxide anion generation, calcium ion flux, and migration.
Summary:
- Platelets enhance PMN bactericidal activity against E. coli.
- Platelets differentially affect PMN superoxide anion (O2-) generation based on stimulation conditions, inhibiting it at rest/low stimulation and enhancing it at optimal stimulation.
- Thrombin-activated platelets and their supernatant induce a transient increase in intracellular calcium ([Ca2+]) in PMN, mediated by factors including ATP and beta-thromboglobulin.
- Platelet supernatant inhibits random migration and chemokinesis of PMN.
Impact:
- This research clarifies the complex interplay between platelets and PMNs.
- Findings contribute to understanding the role of platelet-PMN interactions in inflammatory diseases.
- Identifies specific platelet-derived factors (ATP, beta-thromboglobulin) influencing PMN functions.