Human platelets produce granulocyte-macrophage colony-stimulating factor and delay eosinophil apoptosis.
An association between eosinophils and platelets has been described in several diseases, most notably asthma. Although the mechanisms through which platelets influence eosinophil behavior are not well defined, platelets seem to contribute to the selective accumulation of eosinophils at sites of allergic inflammation by virtue of their ability to produce eosinophil chemotactic factors. We report here for the first time that platelets delay apoptosis, thus enhancing eosinophil survival. A marked inhibition of spontaneous apoptosis was observed using eosinophil:platelet ratios of 1:50, 1:25, 1:10, and 1:5. Moreover, promotion of eosinophil apoptosis by either pronase or dexamethasone was also inhibited greatly in the presence of platelets. The antiapoptotic effect mediated by platelets was dependent on the release of soluble products and was significantly inhibited by neutralizing antibodies directed to GM-CSF. Studies performed by flow cytometry, directed to analyze the cellular source of this cytokine, demonstrated that intracytoplasmic GM-CSF is present in resting platelets. Moreover, GM-CSF was found in platelet supernatants, at concentrations able to prevent eosinophil apoptosis. Our findings support a novel mechanism through which platelets may contribute to eosinophil accumulation at allergic inflammatory sites.
Raiden
Silvina
S
Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina.
Schettini
Jorge
J
Salamone
Gabriela
G
Trevani
Analía
A
Vermeulen
Mónica
M
Gamberale
Romina
R
Giordano
Mirta
M
Geffner
Jorge
J
D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D009500:Neutralization Tests; D011402:Pronase / Q000494:pharmacology
D017304:Annexin A5; D017077:Culture Media, Conditioned; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011402:Pronase; D002118:Calcium