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At least 307 records · Page 17Linked to original sources
PubMed1984

Platelet factor-4 excretion in myeloproliferative disease: implications for the aetiology of myelofibrosis.

Experimental evidence suggests that the fibroblastic proliferation often associated with the myeloproliferative disorders is not part of the neoplastic process, but is secondary to an unknown stimulus. This stimulus may be a factor derived from platelets which promotes the proliferation of fibroblasts in vitro (PDGF). Platelet-derived growth factor is localized to platelet alpha-granules together with PF4 and beta-TG. As an indicator of alpha-granule release, we have measured PF4 levels in plasma, platelets and urine in 46 normal subjects and 49 patients with myeloproliferative disorders, secondary thrombocytosis and miscellaneous malignancies. All 11 patients with elevated urinary PF4 excretion exhibited myelofibrosis, whereas 11 of 22 patients with documented myelofibrosis had urinary PF4 excretion in the normal range. No correlation was seen between marrow fibrosis and plasma levels or the platelet content of PF4. The data are consistent with the possibility that release of mitogen(s) from platelet or megakaryocyte alpha-granules in some patients with myeloproliferative disorders is pathogenetically related to the development of marrow fibrosis.

Blood Platelets↗
PubMed1981

The release of beta-thromboglobulin and platelet factor 4 during extracorporeal circulation for open heart surgery.

Cardiopulmonary bypass is extremely damaging to platelets and it causes a quantitative and qualitative alteration in their functions. We evaluated the release of two platelet-specific proteins, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), in patients who underwent extracorporeal circulation for open heart surgery. A parallel release (basal value beta TG: 119.6 ng/ml, PF4 30 ng/ml) was present for both proteins in a time dependent fashion until the end of extracorporeal circulation. High average levels were observed in patients in whom the bypass was stopped after about 1 h (beta TG 1606 ng/ml, PF4 745 ng/ml) and similarly in those in whom the bypass was stopped after about 2 h (beta TG 1540 ng/ml, PF 4754 ng/ml). No correlation was found either between the level of PF4 and the additional heparin administered after the initial standard dose (r = 0.29, P greater than 0.10) and between the level of PF4 and the amount of heparin consumed during the bypass (r = 0.05, P greater than 0.5).

Beta-Globulins↗
PubMed1992

Cold urticaria as a model of mediator release: platelet factor 4, eosinophil cationic protein and histamine.

Platelet factor 4 (PF4) has previously been linked to precipitation of cold urticaria (CU). The aim of the study was to assess the liberation of PF4, eosinophil cationic protein (ECP) and histamine after cold challenge in patients with CU. Ten controls and 8 patients with CU verified by clinical data and cold challenge test were investigated. Assessment of histamine, ECP and PF4 were done using radioimmunoassays. In patients histamine increased after 10 min on the challenged arm (NS), PF4 increase was statistically significant (p less than 0.05) both in patients and controls. ECP release showed no significant changes. Treatment with doxepin results in clinical improvement, but no changes in mediator release were seen. Thus, in contrast to previous reports an increase of PF4 was seen both in controls as well as in patients. An involvement of ECP was not ascertained. Our data suggest that neither basophils, nor eosinophils or platelets are directly involved in cold urticaria and that mast cell-dependent mediators may be of greater relevance.

Adolescent↗
PubMed2004

Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene expression.

Ets-1 is important for transcriptional regulation in several hematopoietic lineages, including megakaryocytes. Some transcription factors bind to naked DNA and chromatin with different affinities, while others do not. In the present study we used the megakaryocyte-specific promoters platelet factor 4 (PF4), and glycoprotein IIb (GPIIb) as model systems to explore the properties of Ets-1 binding to chromatin. Chromatin immunoprecipitation assays indicated that Ets-1 binds to proximal regions in the PF4 and GPIIb promoters in vivo. In vitro and in vivo experiments showed that Ets-1 binding to chromatin on lineage-specific promoters does not require lineage-specific factors. Moreover, this binding shows the same order of affinity as the binding to naked DNA and does not require ATP-dependent or Sarkosyl-sensitive factors. The effect of Ets-1 binding on promoter activity was examined using the PF4 promoter as a model. We identified a novel Ets-1 site (at -50), and a novel Sarkosyl-sensitive DNase I-hypersensitive site generated by Ets-1 binding to chromatin, which significantly affect PF4 promoter activity. Taken together, our results suggest a model by which Ets-1 binds to chromatin without the need for lineage-specific accessory factors, and Ets-1 binding induces changes in chromatin and affects transactivation, which are essential for PF4 promoter activation.

Adenosine Triphosphate↗
PubMed1989

Identification and characterization of PF4varl, a human gene variant of platelet factor 4.

A synthetic DNA probe designed to detect coding sequences for platelet factor 4 and connective tissue-activating peptide III (two human platelet alpha-granule proteins) was used to identify several similar sequences in total human DNA. Sequence analysis of a corresponding 3,201-base-pair EcoRI fragment isolated from a human genomic library demonstrated the existence of a variant of platelet factor 4, designated PF4var1. The gene for PF4var1 consisted of three exons and two introns. Exon 1 coded for a 34-amino-acid hydrophobic leader sequence that had 70% sequence homology with the leader sequence for PF4 but, in contrast, contained a hydrophilic amino-terminal region with four arginine residues. Exon 2 coded for a 42-amino-acid segment that was 100% identical with the corresponding segment of the mature PF4 sequence containing the amino-terminal and disulfide-bonded core regions. Exon 3 coded for the 28-residue carboxy-terminal region corresponding to a domain specifying heparin-binding and cellular chemotaxis. However, PF4var1 had amino acid differences at three positions in the lysine-rich carboxy-terminal end that were all conserved among human, bovine, and rat PF4s. These differences should significantly affect the secondary structure and heparin-binding properties of the protein based on considerations of the bovine PF4 crystal structure. By comparing the PF4var1 genomic sequence with the known human cDNA and the rat genomic PF4-coding sequences, we identified potential genetic regulatory regions for PF4var1. Rat PF4 and human PF4var1 genes had identical 18-base sequences 5' to the promoter region. The intron positions appeared to correspond approximately to the boundaries of the protein functional domains.

Amino Acid Sequence↗
PubMed1994

Effect of platelet-activating factor and platelet factor 4 on eosinophil adhesion.

The effect of platelet-activating factor (PAF) and platelet factor 4 (PF4) on the adhesion of isolated human eosinophils or eosinophilic cell lines (EoL-1, EoL-3) was examined. Both PAF and PF4 augmented eosinophil adhesion to plates coated with AB plasma or recombinant soluble intercellular adhesion molecule-1 (r-sICAM-1). These findings suggest that PAF and PF4 not only modulate chemotactic activity of eosinophils but also intensify the function of eosinophil adhesion. Since PAF and PF4 induce the expression of adhesion molecules (LFA-1 alpha, LFA-1 beta, CR3) on eosinophils, we could conclude that PAF or PF4 are closely related to eosinophil accumulation not only as chemotactic agents but also as augmentative agents for eosinophil adhesion through involvement in functional eosinophil adherence as well as surface expression of adhesion molecules on eosinophils.

Cell Adhesion↗
PubMedDate not supplied

Amniotic fluid platelet factor 4 and beta-thromboglobulin.

Platelet activating factor (PAF), a powerful platelet activator, has been identified in human embryos and fetuses, and may induce fetal lung maturation. The potential effect of PAF on fetal platelets as indicated by release of beta-thromboglobulin (BTG) and platelet factor 4 (PF4) has not been investigated. We measured BTG and PF4 in amniotic fluid from 78 genetic and 35 pulmonary maturity amniocenteses. BTG and PF4 were higher in the genetic amniocentesis samples (p < 0.001 in each case) than in the lung maturity samples. BTG and PF4 did not correlate with the pulmonary maturity parameters as measured by the lecithin to sphingomyelin ratio and phosphatidylglycerol concentration. Our findings suggest a fetal origin of BTG and PF4 in amniotic fluid.

Amniocentesis↗
PubMed1996

Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension.

Thirteen patients with mild hypertension (untreated diastolic blood pressure of 95 to 114 mmHg) received, in random order, three successive treatments of four weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg daily). At the end of each treatment, blood samples for assessment of platelet aggregation and platelet release of platelet factor 4 (PF4) and for assessment of fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were taken, first at rest, then immediately after five to ten minutes of vigorous exercise, and finally after the subsequent hour of recovery rest. Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with placebo (P < 0.05) at rest, and the threshold for adenosine diphosphate (ADP) aggregation also rose, from 2 microM to 4 (NS). The resting plasma PF4 value fell, although not significantly, during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sampled at rest, and the PF4 plasma levels showed no significant reductions at rest. However, during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy. This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo (P < 0.05). ECLT and t-PA did not shift significantly from the placebo level during either therapy. PAI-1 did not change during spirapril therapy, but during HCT2 treatment it fell, although not significantly, to 9.36 IU/mL from 15.91 with placebo (NS). Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis. HCT2 seems to decrease platelet activity at rest, whereas spirapril seems to some extent to decrease platelet activity at exercise.

Aged↗
PubMed2005

Platelet function and fibrinolytic activity in patients with bronchial asthma.

Platelets have the capacity to release mediators with potent inflammatory or anaphylactic properties. Platelet factor-4 (PF4) and beta-thromboglobulin (BTG) are two of these mediators. On the other hand, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) are two important mediators of fibrinolysis. Both mediators are secreted mainly by vascular endothelium. Plasma levels of PF4, BTG, PAI-1, and tPA may show changes in chronic inflammatory diseases such as asthma. This study examined the role of thrombocytes and the function of the endothelium in asthmatic patients during an attack and during a stable phase. Eighteen patients with known allergic asthma who came to our emergency department with an asthma attack and 14 control subjects were included in the study. Blood samples were taken after starting therapy with salbutamol inhalation. Lung function tests were performed after receiving the first emergency therapy for asthma. Plasma levels of PF4, BTG, PAI-1, tPA were determined before starting steroid therapy and after receiving 1 week of steroid therapy. Plasma levels of PF4 among patients with an asthma attack were significantly higher than those of controls (150.5+/-8.92 IU/mL vs. 92.5+/-7.63 IU/mL, p<0.001). A further increase in plasma PF4 levels was detected after steroid therapy (163.5+/-9.16 IU/mL). Plasma BTG levels of patients on admission were not statistically different from those in the control group (140.4+/-6.34 IU/mL vs. 152.2+/-8.71 IU/mL). An increase was detected after therapy (171.6+/-7.27 IU/mL) and post-treatment plasma levels were statistically meaningful versus the controls. Plasma levels of tPA and PAI were statistically higher than those in controls in asthmatic patients on admission (6.01+/-2.72 vs. 5.4+/-2.3 ng/mL for tPA and 75.2+/-27.2 ng/mL vs. 32.7+/-14.3 ng/mL for PAI-1). Further increases were detected in two parameters after 1 week of therapy with steroids (tPA levels were 6.85+/-2.96 ng/mL and PAI-1 levels were 83.5+/-29.6 ng/mL). There seems to be an increased activity of platelets during an asthma attack. Elevated PAI-1 and tPA levels may also indicate the activated endothelium in asthma. Increases of plasma levels of PAI-1 and tPA after steroid therapy need further investigation because elevated PAI-1 levels enhance airway remodeling.

Adult↗
PubMed2005

Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin.

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti-PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.

Anticoagulants↗
PubMed1992

Detection of platelet-specific protein mRNAs in different megakaryoblasts using the reverse transcriptase polymerase chain reaction.

The short segments of cDNA encoding glycoprotein (GP)Ib alpha, GPIIb, GPIIIa and platelet factor (PF) 4 were amplified using reverse transcriptase-polymerase chain reaction (RT-PCR) in order to characterize various types of megakaryoblasts. Cell lines with megakaryocytic features (K562, CMK and HEL) were tested. GPIb alpha, GPIIb and GPIIIa mRNAs were found to be present in K562, CMK and HEL cells, while only HEL cells expressed PF4 or mRNA. These results suggested that megakaryoblastic cell lines could be categorized into two groups, one with the PF4 transcript and the other without it. PF4 mRNA was present in the cells obtained from one Down's syndrome patient with transient myeloproliferative disorder and in one patient with primary myelofibrosis and megakaryoblastosis. On the other hand, one patient with acute megakaryoblastic leukemia transformed from refractory anemia had a poor prognosis with megakaryoblastic leukemia cells which expressed no PF4 mRNA. These observations suggested that the expression of PF4 mRNA in peripheral blood megakaryoblasts may indicate the absence of a true leukemic process.

Aged↗
PubMed2005

Platelet factor 4 differentially modulates CD4+CD25+ (regulatory) versus CD4+CD25- (nonregulatory) T cells.

Active suppression mediated by CD4(+)CD25(+) T regulatory (Tr) cells plays an important role in the down-regulation of T cell responses to both foreign and self-Ags. Platelet factor 4 (PF4), a platelet-derived CXC chemokine, has been shown to strongly inhibit T cell proliferation as well as IFN-gamma and IL-2 release by isolated T cells. In this report we show that human PF4 stimulates proliferation of the naturally anergic human CD4(+)CD25(+) Tr cells while inhibiting proliferation of CD4(+)CD25(-) T cells. In coculture experiments we found that CD4(+)CD25(+) Tr cells exposed to PF4 lose the ability to inhibit the proliferative response of CD4(+)CD25(-) T cells. Our findings suggest that human PF4, by inducing Tr cell proliferation while impairing Tr cell function, may play a previously unrecognized role in the regulation of human immune responses. Because platelets are the sole source of PF4 in the circulation, these findings may be relevant to the pathogenesis of certain immune-mediated disorders associated with platelet activation, such as heparin-induced thrombocytopenia and autoimmune thrombocytopenic purpura.

Antibodies, Monoclonal↗
PubMed2005

Association of heparin-dependent antibodies and adverse outcomes in hemodialysis patients: a population-based study.

OBJECTIVE: To determine whether some adverse outcomes of hemodialysis could be explained by subclinical heparin-induced thrombocytopenia (HIT). PATIENTS AND METHODS: Platelet factor 4 (PF4)-heparin antibodies were measured by enzyme-linked immunosorbent assay In a population-based cohort of hemodlalysis patients. Participants were then followed up prospectively for thromboembollc events, cardiovascular events, or death. RESULTS: Of the 59 hemodialysis patients residing In Olmsted County, Minnesota, 57 (97%) agreed to study participation. The mean +/- SD age of the patients was 64 +/- 17 years (median hemodialysis duration, 23 months), and 27 (47%) were women. The enzyme-linked Immunosorbent assay was positive for PF4-heparin antibodies in 2 patients (3.5%). The PF4-heparin antibody content varied over a 10-fold range and was not associated with the duration of hemodialysis (P = .99). During a median follow-up of 798 days, 16 thrombotic events, 37 cardiovascular events, and 23 deaths (Including 13 cardiovascular deaths) occurred. After adjusting for the Framingham risk score, the all-cause mortality rate was significantly higher for patients with the highest tertile of PF4-heparln antibody content compared with patients in the lower tertilles (hazard ratio, 2.47; P = .03). Furthermore, 8 (73%) of deaths in this tertile were due to cardiovascular causes (hazard ratio, 4.14; P = .02). CONCLUSIONS: Despite repetitive heparin exposure, the prevalence of HIT In patients undergoing maintenance hemodialysis is no greater than that anticipated for other patient populations. However, to our knowledge, this is the first study to show an association between elevated PF4-heparin antibodies and Increased mortality rates in hemodlalysis patients.

Aged↗
PubMed2000

Human LTC-IC can be maintained for at least 5 weeks in vitro when interleukin-3 and a single chemokine are combined with O-sulfated heparan sulfates: requirement for optimal binding interactions of heparan sulfate with early-acting cytokines and matrix proteins.

We have shown that stromal O-sulfated heparan sulfate glycosaminoglycans (O-S-GAGs) regulate primitive human hematopoietic progenitor cell (HPC) growth and differentiation by colocalizing heparin-binding cytokines and matrix proteins with HPC in stem cell "niches" in the marrow microenvironment. We now show that long-term culture-initiating cells (LTC-IC) are maintained for 5 weeks in the absence of stroma when O-S-GAGs are added to IL-3 and either MIP-1alpha or PF4 (LTC-IC maintenance without GAGs, 32 +/- 2%; with GAGs, 95 +/- 7%; P <.001). When cultured with 5 additional cytokines, O-S-GAGs, IL-3, and MIP-1alpha, LTC-IC expanded 2- to 4-fold at 2 weeks, and 92 +/- 8% LTC-IC were maintained at 5 weeks. Similar results were seen when PF4 replaced MIP-1alpha. Although O-S-GAG omission did not affect 2-week expansion, only 20% LTC-IC were maintained for 5 weeks. When O-S-heparin was replaced by completely desulfated-, N-sulfated (O-desulfated), or unmodified heparins, LTC-IC maintenance at week 5 was not better than with cytokines alone. Unmodified- and O-S-heparin, but not desulfated- or N-sulfated heparin, bound to MIP-1alpha, IL-3, PF4, VEGF, thrombospondin, and fibronectin. However, the affinity of heparin for thrombospondin and PF4, and the association and dissociation rates of heparin for PF4, were higher than those of O-S-heparin. We conclude that (i) although cytokines may suffice to induce early expansion, adult human LTC-IC maintenance for longer than 1 month requires O-S-GAGs, and (ii) HPC support may depend not only on the ability of GAGs to bind proteins, but also on optimal affinity and kinetics of interactions that affect presentation of proteins in a biologically active manner to progenitors. (Blood. 2000;95:147-155)

Adult↗
PubMed2000

Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies.

Antibodies to PF4/heparin can be demonstrated in almost all patients with heparin-induced thrombocytopenia/thrombosis (HIT/HITT) and in some persons exposed to heparin who do not have clinical manifestations. The role of anti-PF4/heparin antibodies in the pathogenesis of HIT/HITT has been difficult to establish because the antibodies found in serum are generally polyclonal and polyspecific. To circumvent this problem, we developed a murine monoclonal antibody (mAb) to human (h) PF4/heparin complexes. A monoclonal IgG(2bkappa )antibody (designated KKO) was identified that bound specifically to hPF4/heparin complexes. Maximal binding of KKO to hPF4/heparin complexes occurred at similar molar ratios of PF4:heparin observed for HIT/HITT antibodies. KKO also bound to hPF4 in association with other glycosaminoglycans. Platelet activation by KKO required heparin and was abrogated by blockade of FcgammaRIIA. In the presence of PF4, KKO bound to endothelial cells, but not to CHO cells lacking heparan sulfate proteoglycans. Variants of PF4 complexed to heparin were recognized equally well by KKO and HIT/HITT sera. KKO competes for binding with a subset of HIT/HITT antibodies that are relatively spared by mutations in the 3rd domain of PF4. The nucleotide and predicted amino acid sequences of KKO and RTO, a murine anti-hPF4 mAb that does not require heparin for binding, revealed no obvious relationship in either the heavy- or the light-chain immunoglobulin variable regions. These studies suggest that KKO recapitulates the antigenic and functional specificity of a subset of HIT/HITT antibodies and may, therefore, provide insight into the pathogenesis of thrombocytopenia and thrombosis in affected persons. (Blood. 2000;95:1533-1540)

Amino Acid Sequence↗
PubMed1992

Genes for beta-thromboglobulin and platelet factor 4 are closely linked and form part of a cluster of related genes on chromosome 4.

The small inducible gene (SIG) family encodes related proteins that are involved in the overlapping processes of coagulation, inflammation, immune response, and wound repair. This family contains two branches, termed CXC and CC, which are distinguished by whether or not the first two of four conserved cysteine residues are separated by an additional amino acid residue. All of the CXC SIGs map to chromosome 4, including those encoding beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), both of which are expressed by megakaryocytes in a tissue-specific fashion. Both of these latter two genes have been previously reported to be duplicated, there being a PF4 and a PF4alt gene, and a beta TG1 and beta TG2 gene. We now show by pulse-field gel electrophoresis (PFGE) that the beta TG genes are closely linked to the PF4 genes and to other previously mapped CXC SIGs, namely IL8 (encoding interleukin-8), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and two related genes GRO2 and GRO3, on a single 700-kb Sfil fragment localized to chromosome bands 4q12-q13. The only CXC SIG not linked to this cluster is that encoding gamma-interferon-induced 10-Kd protein (INP10), which has been previously localized to 4q21. Analysis of lambda genomic clones demonstrate that the beta TG1 and PF4 genes are separated by less than 7 kb, and the beta TG2 and PF4alt genes by approximately 5 kb. Within each beta TG/PF4 duplication, the beta TG-like gene is upstream of its linked PF4-like gene. Thus, the beta TG/PF4 genes appear to form a close-linked complex expressed in a megakaryocyte-specific fashion. Further genomic studies may provide additional insights into the regulation of the tissue-specific expression of the beta TG/PF4 gene complex, while further analysis of the linked CXC SIG cytokine family may provide further understanding of their evolutionary history.

Autoradiography↗
PubMed1991

Inhibition of tumor growth in mice by an analogue of platelet factor 4 that lacks affinity for heparin and retains potent angiostatic activity.

An analogue of human platelet factor 4 (PF4) lacking affinity for heparin was specifically designed to evaluate the importance of this property in the antitumor effects of recombinant PF4. The purified protein, recombinant PF4-241 (rPF4-241), failed to bind heparin but retained the ability to suppress the growth of tumors in mice. Daily intralesional injections of rPF4-241 significantly inhibited the growth of the B-16 melanoma in syngeneic mice without direct inhibitory effects on B-16 cell growth in vitro. Similar antitumor effects were observed with the human colon carcinoma, HCT-116, grown in nude mice, indicating that the inhibitory activity was neither tumor-type specific nor T-cell dependent. rPF4-241 inhibited endothelial cell proliferation in vitro with dose dependence similar to the native sequence rPF4. Both rPF4 and rPF4-241 inhibited angiogenesis in the chicken chorioallantoic membrane. The analogue, however, was inhibitory at lower concentrations than rPF4 in the chorioallantoic membrane system and its inhibitory effects were not abrogated by the presence of heparin. The present findings support the conclusion that both rPF4 and rPF4-241 inhibit tumor growth by suppression of tumor-induced neovascularization. The finding that this activity is independent of heparin binding may allow the development of PF4-based angiostatic agents with reduced toxicity and improved bioavailability. These results also suggest that PF4 may play a more specific role in modulation of blood vessel development than previously recognized.

Amino Acid Sequence↗
PubMed1991

In vivo inhibition of megakaryocyte and platelet production by platelet factor 4 in mice.

The in vivo effect of human platelet factor 4 (PF4) on murine megakaryocytopoiesis and thrombopoiesis was studied. Administration of PF4 induced a dose-dependent decrease in the numbers of megakaryocytes and their progenitor cells (CFU-MK), continuing for 1 week after the injection. However, the size of megakaryocytes and their colonies was not changed following PF4 injection. Platelet levels were significantly decreased at days 3-4. The number of CFU-GM was decreased at days 1-2. White blood cells and hemoglobin were unaffected by PF4. These data indicate that PF4 inhibits megakaryocyte and platelet production in vivo by acting on the early stage of megakaryocyte development.

Animals↗