Altered release of regulated upon activation, normal T-cell expressed and secreted protein from human, normal platelets: contribution of distinct HIV-1MN gp41 peptides
F. Cognasse1,2, H. Hamzeh-Cognasse2, J. Berthet2, P. Damien2, F. Lucht2, B. Pozzetto2, O. Garraud1,2
1Etablissement Français du Sang Auvergne-Loire, Cellule Recherche, Saint Etienne, France, 2Univsersité de Saint Etienne, GIMAP EA3064, Saint Etienne, France
platelets link the processes of haemostasis and inflammation. Platelets can
further, sense danger by the display of e.g. TLR, and our group demonstrated
that they can even discriminate between danger signals in order to secrete
cytokines/chemokines differentially. This study examines the secretion of
normal platelets after exposure to recombinant HIV-1MN -gp120 or gp41 peptides.
Methods: We used
platelets sampled from healthy, HIV-1,2-, normal blood donors. Platelet-Rich
Plasma (PRP), was incubated after addition thrombin receptor agonist peptide) or
HIV env gp. PRP were centrifuged and platelet free supernatant was stored. Two
recombinant gp120MN (produced in insect cells using the baculovirus expression
system) and synthetic peptides of gp41MN, and mAbs to gp41: D50 and 2F5, were
all obtained through the AIDS Research and Reference Reagent Program. Soluble
CD62p and RANTES production in cultures were measured by specific ELISA.
Results: Platelets (n=10)
with various HIV-1MN gp120 or gp41MN peptides had no significant effect on sCD62P
release. None of two recombinant gp120MN tested caused any modulation of RANTES
release. In contrast, the stimulation of platelets with gp41 peptides evidenced
that peptides 2025 (GKLICTTTVPWNASWSNKSL) and 2031 (LLELDKWASLWNWFDITNWL) led
to a significant reduction of RANTES release, whereas the other 8 tested
peptides were ineffective. RANTES production could be significantly restored if
platelet cultures with peptides 2025 and 2031 were performed in the concurrent
presence of D50 or 2F5 mAb anti-gp41.
Conclusions: This data
indicates that certain peptides of HIV env-gp41 exert a negative signal, the
precise nature of which remains to be ascertained and further investigated, for
RANTES production by normal platelets in in vitro stimulation conditions. Our
data provide novel information on possible primary interactions between
platelets and HIV in their early encounter in the circulation. Therefore,
further studies are needed to clarify its consequence: fair or - more likely - foe?
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