Recombinant human macrophage colony-stimulating factor-induced thrombocytopenia in dogs.
To characterize recombinant human macrophage-colony stimulating factor (rhM-CSF)-associated thrombocytopenia (TCP), in vivo studies were performed in dogs, including the biodistributions and recoveries of radiolabelled autologous and allogeneic platelets. rhM-CSF induced a reversible, dose-dependent decrease in platelet counts. The number of megakaryocytes in spleen and marrow of rhM-CSF-treated dogs was increased two to threefold. Recoveries of allogeneic platelets transfused from rhM-CSF-treated donors into tolerized recipients (n = 3) were not significantly different from allogeneic baseline studies (93 +/- 10% of baseline values at 24 h and 90 +/- 1% at 40 h), whereas autologous platelets infused back into rhM-CSF-treated donors had decreased recoveries (45 +/- 2% of baseline values at 24 h, P = 0.03 and 20 +/- 4% at 40 h, P = 0.001). Platelet biodistribution studies showed increased accumulation of radiolabelled platelets over the spleens and livers of rhM-CSF-treated dogs. Histochemistry showed increased levels of platelet-specific antigen (CD41; glycoprotein IIb) associated with Kupffer cells. The sensitivity of platelets from rhM-CSF-treated dogs to activation from thrombin, as measured by expression of P-selectin (CD62P), was not significantly different when compared with baseline studies (P = 0.18; n = 4). These results support the concept that rhM-CSF induces an activation of the monocyte-macrophage system (MMS), which causes a reversible TCP in a dog model.
Abrams
Kraig
K
Puget Sound Blood Center, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA.
Yunusov
Murad Y
MY
Slichter
Sherrill
S
Moore
Peter
P
Nelp
Wil B
WB
Burstein
Samuel A
SA
McDonough
Sean
S
Durack
Lawrence
L
Storer
Barry
B
Storb
Rainer
R
Gass
M John
MJ
Georges
George
G
Nash
Richard A
RA
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002470:Cell Survival; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver; D016173:Macrophage Colony-Stimulating Factor / Q000009:adverse effects*; D010976:Platelet Count; D013154:Spleen; D013921:Thrombocytopenia / Q000139:chemically induced*
D016173:Macrophage Colony-Stimulating Factor