Platelet factor 4

"PF4" redirects here. For SpaceShipTwo PF04, see 2014 Virgin Galactic crash. For USN Tacoma-class patrol frigate, see USS Sausalito (PF-4). For Philippine Navy frigate, see BRP Rajah Lakandula (PF-4). For JMSDF frigate, see JDS Momi (PF-4). For 1997 PF4, see 14967 Madrid. For 1999 PF4, see 38245 Marcospontes. For PF4 receptor, see PF4 receptor.

Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation.^[5] It is usually found in a complex with proteoglycan.

PF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RHP, 1DN3, 1F9Q, 1F9R, 1F9S, 1PFM, 1PFN, 4R9W, 4R9Y, 4RAU
Identifiers
Aliases	PF4, CXCL4, PF-4, SCYB4, platelet factor 4
External IDs	OMIM: 173460; MGI: 1888711; HomoloGene: 87791; GeneCards: PF4; OMA:PF4 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q13.3 Start 73,980,811 bp[1] End 73,982,027 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 E1 Start 90,920,294 bp[2] End 90,921,242 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte trabecular bone granulocyte blood gonad bone marrow testicle bone marrow cell periodontal fiber spleen Top expressed in tibiofemoral joint blood sciatic nerve stroma of bone marrow fetal liver hematopoietic progenitor cell dermis ankle vestibular sensory epithelium carotid body spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cytokine activity heparin binding CXCR3 chemokine receptor binding chemokine activity protein binding Cellular component extracellular region platelet alpha granule lumen extracellular space cytoplasm collagen-containing extracellular matrix Biological process cytokine-mediated signaling pathway chemokine-mediated signaling pathway positive regulation of macrophage differentiation platelet degranulation negative regulation of megakaryocyte differentiation positive regulation of cAMP-mediated signaling negative regulation of MHC class II biosynthetic process leukocyte chemotaxis chemotaxis response to lipopolysaccharide positive regulation of macrophage derived foam cell differentiation positive regulation of gene expression regulation of cell population proliferation immune response positive regulation of tumor necrosis factor production negative regulation of angiogenesis negative regulation of extrinsic apoptotic signaling pathway in absence of ligand inflammatory response positive regulation of transcription by RNA polymerase II negative regulation of cytolysis platelet activation defense response positive regulation of neutrophil chemotaxis antimicrobial humoral immune response mediated by antimicrobial peptide regulation of megakaryocyte differentiation regulation of signaling receptor activity G protein-coupled receptor signaling pathway adenylate cyclase-activating G protein-coupled receptor signaling pathway neutrophil chemotaxis cellular response to lipopolysaccharide Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5196 56744 Ensembl ENSG00000163737 ENSMUSG00000029373 UniProt P02776 Q9Z126 RefSeq (mRNA) NM_002619 NM_001363352 NM_019932 RefSeq (protein) NP_002610 NP_001350281 NP_064316 Location (UCSC) Chr 4: 73.98 – 73.98 Mb Chr 5: 90.92 – 90.92 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Genomics

The gene for human PF4 is located on human chromosome 4.^[6]

Function

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.^[5][7]

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3-B.^[8]

Clinical significance

Antibodies

There are a set of prothrombotic conditions caused by monoclonal antibodies against Platelet factor 4 (anti-PF4) that presents with recurrent thrombosis and persistent thrombocytopenia.^[9][10] At least one author has called these Monoclonal gammopathy of thrombotic significance.

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia (HIT), an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.^[11] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.^[12]

Antibodies against PF4 have been implicated in cases of thrombosis and thrombocytopenia subsequent to vaccination with the Oxford–AstraZeneca or the Janssen COVID-19 vaccine.^[13][14] This phenomenon has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT).^[15]

Expression changes

Changes in the expression of PF4 have been associated with symptoms of long COVID.^[16]

It is increased in patients with systemic sclerosis that also have interstitial lung disease.^[17]

Malaria

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.^[18]

See also

• Platelet-activating factor
• Platelet-derived growth factor