{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPTX3 is a multifunctional soluble pattern‐recognition molecule belonging to the pentraxin family that plays a central role in the humoral arm of innate immunity. Produced locally by diverse cell types—including myeloid cells, endothelial cells, and tissue‐resident stromal cells—it recognizes microbial moieties and modified self‐structures, interacts with complement proteins (such as C1q, factor H, mannose‐binding lectin, and ficolins) and thereby modulates complement activation. In doing so, PTX3 can promote opsonophagocytosis of pathogens and apoptotic cells while fine‐tuning inflammatory responses. This dual capacity for both activating and inhibiting the classical and alternative complement cascades underscores its critical function as a regulatory mediator in innate immune defense."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its antimicrobial properties, PTX3 is intimately involved in cardiovascular and metabolic disorders. In atherosclerosis and vascular inflammation, for instance, PTX3 is expressed by macrophages, endothelial cells, and vascular smooth muscle cells in response to atherogenic stimuli; it modulates tissue factor expression, influences thrombogenesis, and is associated with foam cell transformation, plaque vulnerability, and endothelial dysfunction. Its plasma concentration and tissue expression have been correlated with cardiovascular events, metabolic risk factors, and inflammatory status in diverse clinical settings, suggesting that PTX3 not only serves as a biomarker but also participates in protective or maladaptive vascular remodeling and tissue repair processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "19"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of host defense, PTX3 exerts protective actions against a range of pathogens including fungi, viruses, and bacteria. It is indispensable for antifungal immunity (notably against Aspergillus species), functions as an inhibitor of influenza virus infectivity by interfering with viral glycoproteins, and its gene polymorphisms modulate susceptibility to pulmonary tuberculosis, urinary tract infections, and Pseudomonas colonization in cystic fibrosis. Furthermore, elevated circulating levels of PTX3 have been documented in viral infections such as COVID-19 and serve as strong independent prognostic indicators for mortality, reflecting its rapid induction after infection and tissue injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "28"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPTX3 also plays significant roles in regulating tissue remodeling, angiogenesis, and tumor development. Its interaction with components of the extracellular matrix (for example, through binding to heavy chains of inter‑α‑trypsin inhibitor) is critical for cumulus matrix organization and female fertility. Moreover, by binding fibroblast growth factor‑2, PTX3 antagonizes pro‑angiogenic signals, thereby impacting tumor growth and metastasis; such properties have spurred interest in PTX3-based therapeutic strategies in oncology. Coordinated expression with other extracellular mediators (like TSG‑6) further underscores PTX3’s complex role at the intersection of innate immunity, matrix deposition, and cancer‑related inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "29", "end_ref": "36"}]}, {"type": "t", "text": ""}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eduardo Bonavita, Stefania Gentile, Marcello Rubino, et al. 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