In vivo defibrination results in markedly decreased amounts of fibrinogen in rat megakaryocytes and platelets.
Recently evidence was provided for a pathway whereby circulating fibrinogen enters megakaryocyte granules by an endocytic mechanism. Synthesis of fibrinogen by megakaryocytes has been reported. To determine the relationship between plasma fibrinogen and alpha-granule fibrinogen in megakaryocytes and platelets, the fibrinogen content of these cells was studied in rats defibrinated by use of Ancrod, a thrombinlike enzyme purified from the venom of Agkistrodon rhodostoma. Unlike thrombin, Ancrod does not induce platelet secretion. Rats were injected with Ancrod (50 units/kilogram body weight) at 8-hour intervals for 5 days. There were no significant changes in platelet counts. Blood from the treated rats failed to clot, and plasma fibrinogen levels were less than 15 mg/dl. Bone marrow from defibrinated rats and untreated control rats was stained immunohistochemically for fibrinogen and two other alpha-granule proteins, albumin and platelet factor 4 (PF4), in plastic-embedded sections. The presence of these three proteins in platelets was detected by Western blots. Only trace amounts of fibrinogen were detected in megakaryocytes and platelets from defibrinated rats, but fibrinogen in control megakaryocytes and platelets was readily demonstrated. However defibrinated and control rats did not differ in albumin and PF4 content in megakaryocytes and platelets. It is concluded that a major portion of rat platelet fibrinogen is derived from plasma by endocytosis by megakaryocytes.
Handagama
P J
PJ
Department of Pathology, University of California, San Francisco School of Medicine 94143-0506.
Shuman
M A
MA
Bainton
D F
DF
D000721:Ancrod / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D008533:Megakaryocytes / Q000378:metabolism* / Q000648:ultrastructure; D010976:Platelet Count / Q000187:drug effects; D010978:Platelet Factor 4 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism
D012709:Serum Albumin; D010978:Platelet Factor 4; D005337:Fibrin; D005340:Fibrinogen; D000721:Ancrod