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Cytochalasin D and E: effects on fibrinogen receptor movement and
cytoskeletal reorganization in fully spread, surface-activated platelets: a
correlative light and electron microscopic investigation
OE Olorundare, SR Simmons and RM Albrecht
Department of Pharmacology and Therapeutics, University of Ilorin, Nigeria.
This study investigates the involvement of actin microfilaments in
fibrinogen receptor redistribution and cytoskeletal reorganization that
takes place in fully spread, surface-activated platelets. Colloidal
gold-labeled fibrinogen (Fgn-Au label) in conjunction with video- enhanced
differential interference contrast light microscopy (VDIC) was used to
identify fibrinogen binding sites, glycoprotein IIb/IIIb (GPIIb/IIIa), on
fully spread platelets. Platelets were treated with cytochalasins D and E
(5 x 10(-5) mol/L to 5 x 10(-8) mol/L) for 10 minutes, before or after
incubation with Fgn-Au label. Results observed with VDIC were subsequently
confirmed by high-voltage transmission and low voltage-high resolution
scanning electron microscopic examination of the specimens. Preincubation
of activated platelets with cytochalasin D or E (5 x 10(-5) and 5 x 10(-6)
mol/L) inhibited fibrinogen receptor redistribution and abolished
cytoskeletal reorganization in fully spread platelets. After
surface-activated platelets were incubated with Fgn-Au label, treatment
with the above concentrations of cytochalasin D or E disrupted cytoskeletal
reorganization and caused random movement of previously redistributed
receptor-ligand complexes. Incubation of platelets with cytochalasin E 5 x
10(-6) mol/L prevented platelet activation and spreading. Thus, actin
filaments appear necessary for platelet spreading from the discoid to the
fully spread stage. The ligand-triggered, cytoskeletally directed movement
of fibrinogen receptors in fully spread platelets appears to be dependent
on the presence of intact, polymerized actin. This movement is distinct
from the cytochalasin-insensitive accumulation of GPIIb/IIIa-ligand in the
channels of the open canalicular system.
Volume 79,
Issue 1,
pp. 99-109,
01/01/1992
Copyright © 1992 by The American Society of Hematology
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