Tissue-Specific Expression of Functional Platelet Factor XI Is
Independent of Plasma Factor XI Expression
Chang-jun Hu,
Frank A. Baglia,
David C.B. Mills,
Barbara A. Konkle, and
Peter N. Walsh
From the Departments of Biochemistry and Medicine, The Sol Sherry
Thrombosis Research Center, Temple University School of Medicine,
Philadelphia, PA; and the Cardeza Foundation, Thomas Jefferson
University, Philadelphia, PA.
Platelet factor XI is an alternatively spliced product of the factor
XI gene expressed specifically within megakaryocytes and platelets as
an approximately 1.9-kb mRNA transcript (compared with ~2.1 kb in
liver cells) lacking exon V. Flow cytometry with an affinity-purified
factor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on
activated platelets), and with S12 antibody (to P-selectin, an
-granule membrane protein expressed on the platelet surface during
secretion) on platelets activated with ADP, thrombin, thrombin receptor
peptide (SFLLRN amide), or collagen at various concentrations exposed
platelet factor XI and PAC1 antibody binding in parallel. Unactivated
platelets expressed approximately 40% of total platelet factor XI but
no PAC1 binding sites. Enhanced membrane exposure of platelet factor XI
is independent of
-granule secretion, because ADP and collagen
exposed platelet factor XI but no S12 binding sites. Platelets from
four patients with plasma factor XI deficiency (<0.04 U/mL) had
normal constitutive and activation-dependent expression of platelet
factor XI. Well-washed platelets from normal and from factor
XI-deficient donors incubated with low concentrations of thrombin (0.05 to 0.1 U/mL) corrected the clotting defect observed with factor
XI-deficient plasma. Thus, functionally active platelet factor XI is
differentially expressed on platelet membranes in a tissue-specific
manner both constitutively and in a concentration-dependent fashion by
various agonists in the absence of detectable plasma factor XI.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3800-3807
© 1998 by The American Society of Hematology.