{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:05:21Z","timestamp":1768507521763,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,26]]},"group-title":"Cell Biology","reference-count":69,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The complement receptor CR3, also known as integrin Mac-1 (CD11b\/CD18), is one of the major phagocytic receptors on the surface of neutrophils and macrophages. We previously demonstrated that in its protein ligands, Mac-1 binds sequences enriched in basic and hydrophobic residues and strongly disfavors negatively charged sequences. The avoidance by Mac-1 of negatively charged surfaces suggests that the bacterial wall and bacterial capsule possessing net negative electrostatic charge may repel Mac-1 and that the cationic Mac-1 ligands can overcome this evasion by acting as opsonins. Indeed, we previously showed that opsonization of Gram-negative\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  with several cationic peptides, including PF4 (Platelet Factor 4), strongly augmented phagocytosis by macrophages. Here, we investigated the effect of recombinant PF4 (rPF4) on phagocytosis of Gram-positive\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  in vitro and examined its impact in a mouse model of\n                  <jats:italic>S. aureus<\/jats:italic>\n                  peritonitis. Characterization of the interaction of rPF4 with nonencapsulated and encapsulated\n                  <jats:italic>S. aureus<\/jats:italic>\n                  showed that rPF4 localizes on the bacterial surface, thus making it available for Mac-1. Furthermore, rPF4 did not have direct bactericidal and bacteriostatic activity and was not toxic to host cells. rPF4 enhanced phagocytosis of\n                  <jats:italic>S. aureus<\/jats:italic>\n                  bioparticles by various primary and cultured Mac-1-expressing leukocytes by several folds. It also increased phagocytosis of live nonencapsulated and encapsulated bacteria. Notably, the augmentation of phagocytosis by rPF4 did not compromise the intracellular killing of\n                  <jats:italic>S. aureus<\/jats:italic>\n                  by macrophages. Using a murine\n                  <jats:italic>S. aureus<\/jats:italic>\n                  peritonitis model, we showed that treatment of infected mice with rPF4 caused a significant increase in the clearance of antibiotic-susceptible\n                  <jats:italic>S. aureus<\/jats:italic>\n                  and its methicillin-resistant (MRSA) variant and markedly improved survival. These findings indicate that rPF4 binding to the bacterial surface circumvents its antiphagocytic properties, improving host defense against antibiotic-susceptible and antibiotic-resistant bacteria.\n                <\/jats:p>","DOI":"10.1101\/2023.08.25.554865","type":"posted-content","created":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T04:05:10Z","timestamp":1693109110000},"source":"Crossref","is-referenced-by-count":1,"title":["Platelet Factor 4 (PF4) Improves Survival in a Murine Model of Antibiotic-Susceptible and Methicillin-Resistant\n                  <i>Staphylococcus Aureus<\/i>\n                  Peritonitis"],"prefix":"10.64898","author":[{"given":"Nataly P.","family":"Podolnikova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeryi 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