In vitro assessment of dose-dependent platelet activation by polyclonal antithymocyte globulins: a flow-cytometric analysis.
Polyclonal antithymocyte globulins (ATGs) are immunosuppressive drugs widely used in transplantation and hematologic disorders. Treatment with ATGs can induce side effects such as neutropenia and thrombocytopenia because of unspecific antibodies directed against nonmyeloid cells present in these preparations. Depletion, activation, and expression of adhesion molecules on platelets in vitro were studied in the whole blood of healthy volunteers by means of flow cytometry after incubation with different doses of three polyclonal ATGs. Our data show no ATG-mediated cytotoxic activity against platelets. ATGs are able to induce activation of platelets through increased expression of P-selectin and hLAMP-1 and higher percentages of gated thrombocytes expressing these molecules. Furthermore, increased expression of hLAMP-1 presented a dose-dependent pattern. ATGs induced activation and enhanced expression of adhesion molecules in unstimulated platelets. Increased adhesion may be responsible for undesirable side effects such as thrombocytopenia and reticulopenia.
Beiras-Fernandez
Andres
A
Institute for Surgical Research, Ludwig-Maximilians University, Marchioninistrasse 27, 81377 Munich, Germany.
Walther
Sebastian
S
Muenzing
Silvia
S
Thein
Eckart
E
Hammer
Claus
C
D000961:Antilymphocyte Serum / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008212:Lymphocyte Depletion; D015539:Platelet Activation / Q000187:drug effects*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents