Details

Autor(en) / Beteiligte

• Wiener, E
• Abeyakoon, O
• Benchetrit, G
• Lyall, M
• Keler, T
• Rodeck, C. H.

Titel

Anti-HPA-1a-mediated platelet phagocytosis by monocytes in vitro and its inhibition by Fc gamma receptor (FcγR) reactive reagents

Ist Teil von

• European journal of haematology, 2003-02, Vol.70 (2), p.67-74

Ort / Verlag

Oxford, UK: Munksgaard International Publishers

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• : The study was undertaken to delineate mechanisms of platelet destruction by phagocytosis during fetal/neonatal alloimmune thrombocytopenia (FAIT/NAIT) because of maternal antibodies against human platelet antigen 1a (HPA‐1a). By employing a platelet phagocytosis assay based on the ORPEGEN flow cytometric bacterial phagocytosis test, we measured monocyte ingestion of platelets mediated by anti‐HPA‐1a antibodies. Moreover, we tested, as potential therapeutic agents, FcγR reactive reagents, for their inhibition of this process. Four of six anti‐HPA‐1a sera tested mediated phagocytosis of HPA‐1a‐positive platelets in a concentration‐dependent manner. Monocyte ingestion of platelets was almost completely inhibited by cytochalasin D. No anti‐HPA‐1a‐mediated phagocytosis was observed with anti‐HPA‐1a‐negative platelets. The humanised anti‐FcγRI monoclonal antibody H22 at concentrations 1–100 μg/ml, completely inhibited anti‐HPA‐1a‐mediated phagocytosis as did similar concentrations of ivIg. By contrast, a mouse monoclonal anti‐FcγRII (IV.3, Fab) at 10 μg/ml caused little or no suppression of platelet phagocytosis mediated by two anti‐HPA‐1 sera. Furthermore, the addition of anti‐FcγRII (10 μg/ml) to sub‐optimal concentrations of H22 did not significantly increase the inhibitory effect of the latter compound. Monomeric IgG (0.1–10 μg/ml) failed to suppress anti‐HPA‐1 mediated platelet ingestion by the phagocytes, as did anti‐FcγRIII. To our knowledge this is a rare example of an assay that measures platelet phagocytosis in vitro. The results suggest that FcγRI plays a major role in anti‐HPA‐1a‐mediated platelet phagocytosis by monocytes while FcγRIIa, is of little or minor importance only. Moreover, the findings indicate the use of H22 as an alternative to interavenous Ig (ivIg) in the management of FAIT/NAIT.