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PubMed1981

Plasma concentrations of plbatelet-specific proteins in coronary artery disease.

The plasma concentrations of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured in 100 patients with documented coronary artery disease (CAD) and in 40 controls. 18 patients had had coronary artery bypass surgery (CABS), 25 patients were on therapy with beta-blocking agents and 19 were treated with oral anticoagulants. 38 patients with CAD received neither CABS nor beta-blocking or anticoagulating drugs. The highest plasma concentrations of beta-TG and PF4 were found in the patient group without medical or surgical treatment (patients versus controls: p less 0.01). Patients with CABS showed beta-TG and PF4 levels within the normal range. Patients with beta-blocking agents also had lower beta-TG and PF4 values than the patient group without therapy (p less than 0.05). By contrast, patients on oral anticoagulation therapy presented with similar plasma concentrations of beta-TG and PF4 as untreated patients. Our data indicate that surgical or medical treatment with beta-blocking agents, but not with oral anticoagulants, may have some influence on platelet function in patients with CAD. beta-TG and PF4 radioimmunoassay may be a simple method to study platelet involvement in various diseases and to evaluate possible influences of medical of surgical treatment on in vivo platelet function.

Adrenergic beta-Antagonists↗
PubMed1981

Increased plasma concentrations of platelet factor 4 in coronary artery disease: a measure of in vivo platelet activation and secretion.

Previous studies have shown that there is both a significant shortening in platelet survival and a measured hyperactivity to platelet-aggregating agents in patients with documented coronary artery disease compared with control groups. We used a recently described radioimmunoassay for the platelet-secreted protein platelet factor 4 (PF4) to study 162 patients with documented coronary artery disease. There was a significant increase in plasma PF4 concentrations in patients with documented coronary artery disease compared with angiographically normal patients (8.7 vs 16 ng/ml, respectively, n = 121), but as in previous studies of platelet survival, we could not correlate elevated plasma PF4 concentration and the severity or site of the coronary artery disease. In addition, there was no correlation with left ventricular function, serum cholesterol or the type of angina. Patients with confirmed acute myocardial infarction had no significant difference in mean plasma PF4 concentrations compared with similar groups of coronary disease patients who had prolonged chest pain or chronic stable angina. Coronary artery bypass grafting in a subgroup of patients did not affect the mean plasma PF4 concentration during 1 year of follow-up after bypass surgery, but medical therapy for angina with increasing doses of propranolol and nitrates significantly reduced PF4 concentration in another subgroup of patients who were not considered to be candidates for surgical therapy.

Angina Pectoris↗
PubMed1992

Platelet factor 4 efficiently reverses heparin anticoagulation in the rat without adverse effects of heparin-protamine complexes.

BACKGROUND: It has been observed that the reversal of heparin anticoagulation in humans by protamine sulfate (PS) results in various adverse reactions including leukopenia, thrombocytopenia, activation of complement, increased vascular permeability, systemic hypotension, pulmonary vasoconstriction, and pulmonary edema. The purpose of this study was to compare the efficacy and effects of native platelet factor 4 (PF4) and recombinant platelet factor 4 (rPF4) with those of PS in heparin neutralization in vivo, using a rat model. METHODS AND RESULTS: Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the right femoral vein and carotid artery were cannulated. For determination of activated partial thromboplastin time, platelet count, white blood cell count, and complement titer, arterial blood samples were taken before and immediately after heparin (10 units/100 g) infusion and at several time points after the infusion of the neutralizing agent (PS, 0.1 mg/100 g; PF4, 0.5 mg/100 g). In separate groups of animals, mean arterial blood pressure was monitored throughout identical protocols and the lungs were prepared for histological examination. The anticoagulant activity of heparin was effectively reversed by all of the neutralizing agents (PS, PF4, and rPF4). Platelet count (48% of initial), white blood cell count (52% of initial), complement titer (60% of initial), and mean arterial pressure (20% decrease) decreased significantly in heparinized animals receiving PS but not in those receiving PF4 or rPF4. Lung interstitium appeared normal when heparin was followed by PF4; however, interstitial edema and hemorrhage were observed with heparin-PS. CONCLUSIONS: These results suggest that PF4 efficiently reverses heparin anticoagulation in the rat without the adverse effects of heparin-protamine complexes. Therefore, rPF4 may be an appropriate substitute for PS in patients undergoing cardiovascular surgery and other procedures that require heparin anticoagulation.

Animals↗
PubMed1999

Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia.

BACKGROUND: Cardiopulmonary bypass (CPB) induces platelet activation with release of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development of antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU. kg-1. d-1) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily) (group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients (61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thrombocytopenia was observed in subjects receiving LMWH, although 2 had high levels of antibodies with positive serotonin release assay results. When antibodies to H-PF4 were present, mean platelet counts were lower only in patients with FcgammaRIIA R/R131 platelets. CONCLUSIONS: These results provide evidence that the development of antibodies to H-PF4 after CPB performed with UFH is not influenced by the postoperative heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients continuously treated with UFH.

Adolescent↗
PubMed1994

Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells.

Heparin-induced thrombocytopenia/thrombosis (HITP) is thought to be mediated by immunoglobulins that activate platelets in the presence of pharmacologic concentrations of heparin, but the molecular basis for this relatively common and often serious complication of heparin therapy has not been established. We found that plasma from each of 12 patients with HITP contained high titer (> or = 1:200) antibodies that reacted with immobilized complexes of heparin and platelet factor 4 (PF4), a heparin-binding protein contained in platelet alpha-granules. Recombinant human PF4 behaved similarly to PF4 isolated from platelets in this assay system. Complexes formed at an apparent heparin/PF4 molecular ratio of approximately 1:2 (fresh heparin) and approximately 1:12 (outdated heparin) were most effective in binding antibody. Immune complexes consisting of PF4, heparin, and antibody reacted with resting platelets; this interaction was inhibited by a monoclonal antibody specific for the Fc gamma RII receptor and by excess heparin. Human umbilical vein endothelial cells, known to express heparin-like glycosaminoglycan molecules on their surface, were recognized by antibody in the presence of PF4 alone; this reaction was inhibited by excess heparin, but not by anti-Fc gamma RII. Antibodies reactive with heparin/PF4 were not found in normal plasma, but IgG and IgM antibodies were detected at dilutions of 1:10 (IgG) and 1:50 (IgM) in 3 of 50 patients (6%) with other types of immune thrombocytopenia. These findings indicate that antibodies associated with HITP react with PF4 complexed with heparin in solution or with glycosaminoglycan molecules on the surface of endothelial cells and provide the basis for a new hypothesis to explain the development of thrombocytopenia with thrombosis or disseminated intravascular coagulation in patients sensitive to heparin.

Antibodies↗
PubMed2024

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria.

BACKGROUNDFeatures of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.METHODSPlasma from children with uncomplicated malaria (UM) (n = 124) and CM (n = 136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-platelet factor 4/polyanion (anti-PF4/P), anti-phospholipid, anti-phosphatidylserine, anti-myeloperoxidase, anti-proteinase 3, anti-dsDNA, anti-&#x3b2;-2-glycoprotein I, and anti-cardiolipin. Plasma samples from individuals with nonmalarial coma (NMC) (n = 49) and healthy controls (HCs) (n = 56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.RESULTSMedian anti-PF4/P and anti-PS IgG levels were elevated in individuals with malaria infection relative to levels in HCs (P < 0.001) and patients with NMC (PF4/P: P < 0.001). Anti-PF4/P IgG levels were elevated in children with CM (median = 0.27, IQR: 0.19-0.41) compared with those with UM (median = 0.19, IQR: 0.14-0.22, P < 0.0001). Anti-PS IgG levels did not differ between patients with UM and those with CM (P = 0.39). When patients with CM were stratified by malaria retinopathy (Ret) status, the levels of anti-PF4/P IgG correlated negatively with the peripheral platelet count in patients with Ret+ CM (Spearman's rho [Rs] = 0.201, P = 0.04) and associated positively with mortality (OR = 15.2, 95% CI: 1.02-275, P = 0.048). Plasma from patients with CM induced greater platelet activation in an ex vivo assay relative to plasma from patients with UM (P = 0.02), and the observed platelet activation was associated with anti-PF4/P IgG levels (Rs= 0.293, P = 0.035).CONCLUSIONSThrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.

Child↗
PubMed2003

Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene.

Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We previously reported that GATA-1 and ETS-1 regulate the rat PF4 promoter and transactivate the PF4 gene. For the present study, we investigated the regulatory elements and their transcription factors responsible for the lineage-specific expression of the PF4 gene. The promoter activities of deletion constructs were evaluated, and a novel regulatory element termed TME (tandem repeat of MEIS1 binding element) (-219 to -182) was defined. Binding proteins to TME were strongly detected in HEL nuclear extracts by electrophoresis mobility shift assay (EMSA), and they were purified by DNA affinity chromatography. By performing Western blottings and supershift assays, the binding proteins were identified as homeodomain proteins, MEIS1, PBX1B, and PBX2. These factors are expressed in megakaryocytes differentiated from CD34+ cells in human cord blood. MEIS1 and PBXs bind to the TME as MEIS1/PBX complexes and activate the PF4 promoter. In nonmegakaryocytic HepG2 cells, GATA-1 and ETS-1 activate the PF4 promoter approximately 10-fold. Surprisingly, we found that additional expression of both MEIS1 and PBX2 multiplied this major activation another 2-fold. This activation was not observed when MEIS1 binding sites in the TME were disrupted. Furthermore, inhibition of the binding of endogenous MEIS1/PBX complexes to the TME decreased the promoter activity by almost one half, in megakaryocytic HEL cells. Thus, these studies demonstrate that the homeodomain proteins, MEIS1, PBX1B, and PBX2, play an important role in megakaryocytic gene expression.

Animals↗
PubMed2004

Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-kappaB-dependent manner.

The involvement of platelets in the pathogenesis of atherosclerosis has recently gained much attention. Platelet factor 4 (PF4), a platelet-specific chemokine released on platelet activation, has been localized to atherosclerotic lesions, including macrophages and endothelium. In this report, we demonstrate that E-selectin, an adhesion molecule involved in atherogenesis, is up-regulated in human umbilical vein endothelial cells exposed to PF4. Induction of E-selectin RNA is time and dose dependent. Surface expression of E-selectin, as measured by flow cytometry, is also increased by PF4. PF4 induces E-selectin expression by activation of transcriptional activity. Activation of nuclear factor-kappaB is critical for PF4-induced E-selectin expression, as demonstrated by promoter activation studies and electrophoretic mobility shift assays. Further, we have identified the low-density lipoprotein receptor-related protein as the cell surface receptor mediating this effect. These results demonstrate that PF4 is able to increase expression of E-selectin by endothelial cells and represents another potential mechanism by which platelets may participate in atherosclerotic lesion progression.

Arteriosclerosis↗
PubMed2001

Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia.

The pathogenesis of thrombosis in heparin-induced thrombocytopenia (HIT) was studied by investigating whether antibodies to heparin-platelet factor 4 (H-PF4) induced tissue factor (TF) synthesis by monocytes. Plasma from 5 patients with HIT containing IgG to H-PF4 was incubated with peripheral blood mononuclear cells without or with purified PF4 and heparin. Significant TF-dependent procoagulant activity (PCA) expressed by monocytes, measured with a factor Xa-based chromogenic assay, was induced after incubation of each HIT plasma sample. This monocyte PCA required the presence of PF4 and was inhibited by high concentrations of heparin. Furthermore, purified HIT IgG added to whole blood with PF4 and heparin also provoked significant synthesis of TF mRNA by monocytes, demonstrated by RT-PCR, and this effect was not observed with normal IgG. These findings strongly support the hypothesis that antibodies to PF4 developed in HIT trigger the production of tissue factor by monocytes, and this effect could account in vivo for hypercoagulability and thrombotic complications in affected patients.

Blood Coagulation↗
PubMed1999

Short-term effect of exercise on platelet factor 4 in normal subjects and in patients with coronary artery disease.

BACKGROUND: The aim of this study was to evaluate the plasma concentration of a platelet-derived protein, platelet factor 4 (PF4), before and after exercise in coronary artery disease. METHODS: We enrolled 60 patients with documented ischemic heart disease. The subjects were divided into two groups: Group 1 patients with previous myocardial infarction (n = 20, 13 males, 7 females, mean age 51.6 +/- 7.5 years, range 38-62 years); Group 2 patients with exercise-induced angina (n = 40, 22 males, 18 females, mean age 52.6 +/- 8.0 years, range 38-65 years). Patients with hypertension, hyperlipidemia and diabetes were excluded. Patients with angina or ST segment depression during the stress test were included in a subgroup (n = 33, 21 males, 12 females, mean age 50.3 +/- 6.3 years, range 40-65 years). Twenty healthy subjects without coronary risk factors (13 males, 7 females, mean age 53.2 +/- 7.1 years, range 38-65 years) served as controls. PF4 was measured in all patients at baseline and 5 min after a bicycle exercise test. Plasma PF4 levels were measured performed by radioimmunoassay (ng/ml, normal range 0-10). RESULTS: Patients with ischemic heart disease showed a high basal concentration of PF4 compared with controls. PF4 levels at baseline vs after stress test were 4.1 +/- 2.5 vs 5.3 +/- 2.6 ng/ml in healthy subjects; 33.4 +/- 15.8 vs 56.2 +/- 28.2 ng/ml (p < 0.001) in Group 1; 22.4 +/- 15.8 vs 44.6 +/- 28.4 ng/ml (p < 0.001) in Group 2; 29.9 +/- 15.5 vs 67.7 +/- 26.1 ng/ml in the subgroup with angina or ST segment depression (p < 0.001), and 23.1 +/- 16.5 vs 26.0 +/- 18.1 ng/ml in those without angina or ST segment depression (NS). CONCLUSIONS: These findings support the hypothesis that a significant increase in PF4 levels after exercise is associated with clinically significant coronary artery disease.

Adult↗
PubMed2002

[Transfer of cDNAs of platelet factor 4 and N-truncated peptide inhibits solid tumor growth in vivo].

OBJECTIVE: Determine the anti-tumor angiogenic effect of PF4 and p17 - 70 using virally mediated gene transfer. METHODS: Full-length PF4 cDNA and p17 - 70 cDNA were cloned into retroviral vector (pLXSN). KB was incubated with the supernatant of transfected PA317. PCR, RT-PCR and Western blotting analysis was used to determine the integration and expression of foreign gene. By MTT method the effects of the supernatants of PA317-PF4s and KB-PF4s on the proliferation of human umbilical vein endothelial cells (HUVEC) were studied. Tumorigenecity of KB-PF4 and KBp17 - 70 cells was assayed with xenograft tumor growth in isogenous nude mice by examining the growth rate of xenograft, survival, and histochemistry of xenograft tumor. RESULTS: Recombinant PF4 and p17 - 70 were able to inhibit selectively HUVEC proliferation. Animal survival was significantly prolonged. Furthermore, p17 - 70 significantly prolonged animal survival compared with PF4 group (P < 0.05). CONCLUSION: Transduction of p17 - 70 inhibits solid tumor growth through an anti-angiogensis mechanism. Targeted anti-angiogenesis, using retroviral-mediated PF4 gene transfer, especially p17 - 70 represents a promising strategy for cancer gene therapy.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Platelet factor 4 gene transfection into tumor cells inhibits angiogenesis, tumor growth and metastasis.

Tumor growth and metastasis depend on angiogenesis, which is triggered by a chemical signal from the tumor cells to resting endothelial cells which then enter into a phase of rapid growth. Platelet Factor 4 (PF4) inhibits endothelial proliferation in vitro and angiogenesis in vivo. PF4 also inhibits tumor growth, however, as with other angiogenesis inhibitors, sustained tumor growth inhibition requires prolonged exposure to the recombinant protein. In this study, Lewis lung carcinoma (LLH) cells were transfected with the human PF4 via mammalian expression vectors and the ability of the transfected cells to form tumors and metastasis in vivo was evaluated. To evaluate the tumor growth rate of PF4-transfected (LLH/PF4) or control (LLH/neo) cells in vivo, we injected LLH/PF4 or LLH/neo cells subcutaneously (s.c.) or intravenously (i.v.). In the s.c. assay, LLH/PF4 had no significant effect on tumor growth. Conversely, in the i.v. assay, PF4 significantly reduced the number of lung metastasis (p=0.019) and weight (p=0.056). The inhibition of lung metastasis suggests that PF4 may inhibit tumor-associated neovascularization, and may prevent the affinity of tumor cells for the normal lung tissue.

Animals↗
PubMed1990

Biologic and biochemic properties of recombinant platelet factor 4 demonstrate identity with the native protein.

Platelet factor 4 (PF4) is a 70 amino acid protein released from the alpha-granules of platelets after activation. The exact biologic function of this protein is unknown. We have constructed an expression vector for recombinant PF4 (rPF4) in the T7-based promoter vector pT7-7 to better study the relationship between PF4 structure and function. The protein was expressed in Escherichia coli and purified to homogeneity by heparin-agarose affinity chromatography and reverse-phase high-performance liquid chromatography. Purity of protein was confirmed by immunoblot analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which resulted in a single component with a molecular weight of 8,000 daltons. The amino acid composition and sequence of the N-terminal 20 residues showed that rPF4 is identical to PF4 prepared from human platelets (hPF4), except for an N-terminal initiating methionine residue. Immunoblots revealed that rPF4 and hPF4 bound polyclonal anti-hPF4 equally well, while chemotaxis experiments demonstrated similar potencies as neutrophil attractants. Dose-dependent neutrophil chemotactic responses and competitive studies with polyclonal anti-hPF4 antiserum further demonstrate similar chemotactic properties of the two PF4 species. In conclusion, our data show that this recombinant protein and the native protein appears to have similar immunologic, heparin-binding, and chemotactic properties. The chemotactic properties of hPF4 appear to be entirely intrinsic to the protein and not due, in part, to any contaminating protein. Furthermore, our expression vector should prove useful for the construction of recombinant forms of PF4 to investigate structure/function relationships of this biologically important protein.

Amino Acid Sequence↗
PubMed1983

Standardization of beta-thromboglobulin and platelet factor 4: a collaborative study to investigate the sources and extent of variation in the measurement of platelet specific proteins.

A collaborative study involving seven laboratories has been carried out to investigate the sources and extent of variation in the measurement by radioimmunoassay of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). Three plasma samples, one purified beta-TG sample and two purified PF4 samples were assayed against house standards for the respective antigens by each laboratory. The main source of variation of both beta-TG and PF4 measurements was inter-assay (particularly for PF4). It was found that a significant component of this variation was due to the participants' use of different preparations as house standards for beta-TG and for PF4. This indicates that the first step in the standardization of beta-TG and PF4 measurement should be the introduction of a reference for each.

Beta-Globulins↗
PubMed1980

Secreted platelet proteins with antiheparin and mitogenic activities in chronic renal failure.

The levels of secreted platelet antigen (LA-PF4/beta TG) were measured by radioimmunoassay in samples of PPP obtained from human blood collected on EDTA and inhibitors of platelet release reaction. These levels in plasma of 17 normal individuals, 18 nondialyzed patients with chronic renal failure, and nine patients on hemodialysis were 31.9 +/- 2.8 ng/ml, 135.1 +/- 21.4, and 291.8 +/- 26.3, respectively. No significant differences were observed in platelet counts and in the levels of this antigen in PRP of these three groups of individuals. The levels of PF4 in PPP of eight normal individuals and in plasma of seven patients with chronic renal failure were 7.41 +/- 0.67 and 7.53 +/- 1.11 ng/ml, respectively. During processing of blood samples in the absence of platelet release inhibitors, platelets of patients with chronic renal failure released less LA-PF4/beta TG antigen than did normal platelets. The mean levels of LA-PF4/beta TG antigen excreted in urine of six normal individuals and 10 patients with chronic renal failure were 57.75 and 1461.5 ng/100 mg of creatinine per day, respectively. After 3 hr hemodialysis, LA-PF4/beta TG antigen levels in PPP increased from 291.8 +/- 26.3 ng/ml to 505.3 +/- 87.3. By contrast, this antigen in three patients with successful kidney transplants rapidly returned to levels close to normal following graft function. Immunoreactive material from pooled urine of patients with chronic renal failure was isolated by isoelectric focusing. This material focused at pH 10.0 to 10.8 and induced DNA biosynthesis in 3(3 swiss cells, indicating its similarity to PBP. It is proposed that elevation of LA-PF4/beta TG antigen observed in plasma of patients with chronic renal failure resulted from the impaired handling of this protein by the kidney.

Adult↗
PubMed1995

Chemokine regulation of human megakaryocytopoiesis.

We have previously shown that platelet factor 4 (PF4), a platelet-specific CXC chemokine, can directly and specifically inhibit human megakaryocyte colony formation. We therefore hypothesized that PF4 might function as a negative autocrine regulator of megakaryocytopoiesis. Herein we present additional studies characterizing the inhibitory effect of CXC chemokines on human megakaryocyte development. We first corroborated our initial studies by showing that recombinant human (rH) PF4, like the native protein, inhibited megakaryocytopoiesis. We then examined the inhibitory properties of other CXC family members. Neutrophil activating peptide-2 (NAP-2), a naturally occurring N-terminally cleaved beta TG peptide, was found to inhibit megakaryocytopoiesis with two to three orders of magnitude greater potency than PF4. Structure function studies showed that an N-terminal mutation, which eliminated NAP-2's neutrophil activating properties (NAP-2E2-->A), also abrogated its ability to inhibit megakaryocyte development. Further investigations of this type demonstrated that a chimeric PF4 protein (AELR/PF4) in which PF4's N-terminus was replaced with the first four amino acids of NAP-2 was also a potent inhibitor of megakaryocytopoiesis. Interleukin (IL)-8, another CXC chemokine, and three CC chemokines (macrophage inhibitory protein-1 alpha [MIP-1 alpha], MIP-1 beta, and C10) also specifically inhibited megakaryocyte colony formation at NAP-2 equivalent doses. CXC and CC chemokine inhibition was additive suggesting that the effects might be mediated through a common pathway. The inhibitory effects of NAP-2 and MIP-1 alpha could not be overcome by adding physiologically relevant amounts of recombinant human megakaryocyte growth and development factor (MGDR) (50 ng/mL) to the cultures. Using Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) based analyses, we documented mRNA expression of IL-8 receptor isoforms alpha and beta in total platelet RNA and in normal human megakaryocytes, respectively. Based on these results, we hypothesize that chemokines play a physiologic role in regulating megakaryocytopoiesis. Because chemokines are elaborated by ancillary marrow cells, both autocrine and paracrine growth control is suggested, the effects of which might be exerted, in part, through alpha and beta IL-8 receptors.

Amino Acid Sequence↗
PubMed1993

Lack of increase or reduction in circulating platelet factor 4 and heparin-releasable platelet factor 4 in symptomatic patients with asthma.

We measured circulating platelet factor 4 (PF4) and heparin-releasable platelet factor 4 (HR-PF4) in 13 symptomatic patients suffering from bronchial asthma and in 10 matched normal controls. Neither a difference between patients and controls, nor a correlation between platelet count and HR-PF4 was found (PF4: controls 2.1 +/- 2.9; patients 3.6 +/- 4.4 ng/ml (n.s.); HR-PF4: controls 127 +/- 49, patients 101 +/- 34 ng/ml (n.s.). Therefore, the pathogenetic role of PF4 in the mechanism of bronchial asthma, elsewhere hypothesized, cannot definitely be established.

Adult↗
PubMed1995

Effects of antithrombin III and antivenom on procoagulant activity of Russell's viper venom in a whole blood model.

The procoagulant activities of Russell's viper venom were assessed in an in vitro whole blood model. Sequential samplings showed that the generation of fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4 (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an initial slow phase followed by a rapid phase of secretion. In the presence of Russell's viper venom, the generation of both FPA and PF4 was accelerated with the bi-phasic kinetics of PF4 being maintained while that of FPA completely disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin III (AT-III) had no antagonistic effect against the venom but combination of both resulted in a significant prolongation of both FPA and PF4 release (p < 0.05). High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics and serial levels of both parameters were lower than those treated with the combined regimen, although these were not statistically significant. Unlike the untreated venom activated whole blood, there was no clot formation following treatment with either the combined regimen or high dose AT-III. The results of this study suggested that the effect of Russell's viper venom on the clotting cascade is more potent and direct than that on platelet activity. There were complementary effects between antivenom and AT-III is controlling of both FPA and PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT-III alone when administered in a sufficient dose, abolished the procoagulant effects of Russell's viper venom.

Animals↗