Platelet factor

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Factor V. High in sialic acid content. Factor V is a large asymmetric single-chain glycoprotein that becomes an active participant in the coagulation cascade when it is converted to its active form by a-thrombin. Approximately 25% of human Factor V is found in the whole blood associated with platelets. Factor V is an essential cofactor along with Factor Xa plus phosphohpid plus Ca " in the conversion of prothrombin to thrombin. 

Heparin-induced thrombocytopenia A clinical syndrome of IgG antibody production against the heparin-platelet factor 4 complex occurring in approximately 1% to 5% of patients exposed to either heparin or low-molecular-weight heparin. Heparin-induced thrombocytopenia results in excess production of thrombin, platelet aggregation, and thrombocytopenia (due to platelet clumping), often leading to venous and arterial thrombosis, amputation of extremities, and death. 

St Charles R, Walz DA, Edwards BF. The three-dimensional structure of bovine platelet factor 4 at 3.0-A resolution. J Biol Chem 1989 264 2092-9. 

Mayo KH, Ilyina E, Roongta V, et al. Heparin binding to platelet factor-4. An NMR and site-directed mutagenesis study arginine residues are crucial for binding. Biochem J 1995 312 357-65. 

Stuckey JA, St Charles R, Edwards BF. A model of the platelet factor 4 complex with heparin. Proteins 1992 14 277-87. 

Lasagni L, Francalanci M, Annunziato F, et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 2003 197(11) 1537—1549. 

Maione TE, Gray GS, Petro J, et al. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science 1990 247(4938) 77-79. 

Bikfalvi A, Gimenez-Gallego G. The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules. Semin Thromb Hemost 2004 30(1) 137-144. 

Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M. Structural and functional comparison of the genes for human platelet factor 4 and PF4alt. Blood 1990 76(2) 336-344. 

Green CJ, Charles RS, Edwards BF, Johnson PH. Identification and characterization of PF4varl, a human gene variant of platelet factor 4. Mol Cell Biol 1989 9(4) 1445-1451. 

Struyf S, Burdick MD, Proost P, Van Damme J, Stricter RM. Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res 2004 95(9) 855-857. 

Brandt E, Petersen F, Fudwig A, Ehlert JE, Bock L, Flad HD. The beta-thrombo-globulins and platelet factor 4 blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation. J Feukoc Biol 2000 67(4) 471 178. 

Gentilini G, Kirschbaum NE, Augustine JA, Aster RH, Visentin GP. Inhibition of human umbilical vein endothelial cell proliferation by the CXC chemokine, platelet factor 4 (PF4), is associated with impaired downregulation of p21(CiplAVAFl). Blood 1999 93(1) 25—33. 

Sulpice E, Bryckaert M, Lacour J, Confreres JO, Tobelem G. Platelet factor 4 inhibits FGF2-induced endothelial cell proliferation via the extracellular signal-regulated kinase pathway but not by the phosphatidylinositol 3-kinase pathway. Blood 2002 100(9) 3087-3094. 

Perollet C, Han ZC, Savona C, Caen JP, Bikfalvi A. Platelet factor 4 modulates fibroblast growth factor 2 (FGF-2) activity and inhibits FGF-2 dimerization. Blood 1998 91(9) 3289-3299. 

Dudek AZ, Nesmelova I, Mayo K, Verfaillie CM, Pitchford S, Slungaard A. Platelet factor 4 promotes adhesion of hematopoietic progenitor cells and binds IL-8 novel mechanisms for modulation of hematopoiesis. Blood 2003 101(12) 4687-4694. 

Deuel TF, Keim PS, Farmer M, Heinrikson RL. Amino acid sequence of human platelet factor 4. Proc Natl Acad Sci U S A 1977 74 2256-2258. 

Fig. 2. The intrinsic and extinsic cascade coagulation systems. activation -I, inhibition HMK, high molecular kininogen Cl-inh., complement-1 esterase inhibitor AT-III, antithrombin HI a 1 -PI, alpha-1 protein inhibitor pf-3, platelet factor 3.

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