Role of complement-derived peptides in thrombocytopenia elicited by soluble aggregates of immunoglobulin G in the rat.
The variations in platelet counts upon intravenous challenge with soluble aggregates of IgG were assessed in normal rats. A time- and dose-dependent thrombocytopenia, followed by recovery to preinfusion values after 30 minutes was observed. Rats injected with immune aggregates showed an increase in plasma levels of immunoreactive thromboxane B2, however, this increase was delayed as compared with the peak level of the thrombocytopenia. Previous treatment of rats with either indomethacin or aspirin, inhibited thromboxane B2 release, but did not affect thrombocytopenia. Pretreatment of the animals with BN 52021, a potent antagonist of platelet-activating factor binding to its receptor, also failed to block thrombocytopenia. Complement depletion by prior treatment with cobra venom factor, caused a significant reduction of the thrombocytopenia, whereas DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, an inhibitor of carboxypeptidase N, potentiated the thrombocytopenia elicited by submaximal doses of either IgG aggregates or a homogeneous preparation of rat anaphylatoxin containing C5a. In addition, rats challenged with doses of IgG aggregates higher than 5 mg/kg showed a massive complement consumption coincident with the onset of thrombocytopenia. "In vitro" aggregation/secretion experiments with rat platelets showed little platelet-stimulating activity either by aggregated IgG through the Fc receptor or through the CR1 receptor. By contrast, a preparation of rat serum anaphylatoxins containing C5a, showed a high platelet-secreting activity. These data suggest that a complement-derived peptide(s), most probably C5a, is one of the effector substances for platelet activation in response to soluble aggregates of IgG.
Fernandez-Gallardo
S
S
Instituto de Investigaciones Medicas de la Fundacion Jimenez Diaz, Centro Asociado al CSIC, Madrid, Spain.
Gijon
M A
MA
Furio
V
V
Vivanco
F
F
Crespo
M S
MS
D000706:Anaphylatoxins / Q000502:physiology*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a; D007074:Immunoglobulin G / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D010976:Platelet Count; D051381:Rats; D011919:Rats, Inbred Strains; D013921:Thrombocytopenia / Q000209:etiology* / Q000276:immunology; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D000706:Anaphylatoxins; D000936:Antigen-Antibody Complex; D003182:Complement C5; D007074:Immunoglobulin G; D010455:Peptides; D013929:Thromboxane B2; D013928:Thromboxane A2; D015936:Complement C5a