Tissue-specific expression of functional platelet factor XI is independent of plasma factor XI expression.
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 approximately 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 alpha-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 alpha-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.
Hu
C J
CJ
Departments of Biochemistry and Medicine, The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
Baglia
F A
FA
Mills
D C
DC
Konkle
B A
BA
Walsh
P N
PN
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D005172:Factor XI / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005173:Factor XI Deficiency / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism*; D008875:Middle Aged; D009928:Organ Specificity; D019007:P-Selectin / Q000276:immunology; D015539:Platelet Activation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D005172:Factor XI