Proplatelet basic protein (PPBP)

Proplatelet basic protein (PPBP), also known as CXCL7, is a member of the CXC chemokine family primarily stored in the alpha-granules of platelets (UniProt P02775). Upon platelet activation, PPBP is released and undergoes N-terminal proteolytic processing by enzymes such as cathepsin G and thrombin to form active peptides, including connective tissue-activating peptide III (CTAP-III), beta-thromboglobulin (beta-TG), and neutrophil-activating peptide 2 (NAP-2) (NCBI Gene 5473). These derivatives, particularly NAP-2, are potent chemoattractants and activators for neutrophils, mediating their recruitment to sites of injury or inflammation through the activation of CXCR1 and CXCR2 receptors (PMID: 15507527). Beyond its role in acute inflammation, PPBP is involved in stimulating DNA synthesis, mitosis, and glycolysis in fibroblasts, as well as promoting angiogenesis in tumor environments (PMID: 22490440). In clinical contexts, elevated levels of PPBP and its derivatives are associated with various inflammatory conditions, cardiovascular diseases like atherosclerosis, and the progression of several cancers, where they facilitate tumor growth and metastasis. While direct inhibitors of the PPBP protein are currently in preclinical development, the PPBP signaling pathway is primarily modulated through the use of CXCR1 and CXCR2 antagonists in clinical trials for inflammatory and oncological indications.

Other names

CXCL7Neutrophil-activating peptide 2NAP-2Connective tissue-activating peptide IIICTAP-IIIBeta-thromboglobulinBeta-TGSmall inducible cytokine subfamily B member 7SCYB7Platelet basic proteinPBPThrombocidin-1Thrombocidin-2TGB1B-TG1

Antagonism of CXCR1 and CXCR2 receptors to block PPBP-mediated signaling and neutrophil recruitment.