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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Platelets interact with leukocytes to fine-tune their functions, thus providing essential regulation of (patho-) physiologic immune responses in various diseases. Circulating platelet-leukocyte aggregates (PLAs) represent a sensitive biomarker to estimate disease severity both in patients and murine models. However, a limited understanding of the sensitivity of PLA measurements to methodological variables may undermine their accuracy and comparability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To elucidate how blood draw techniques, anticoagulation, processing delay and assay temperature affect murine platelet-leukocyte interactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Murine blood was obtained via retro-orbital, <jats:italic>vena cava<\/jats:italic> or cardiac puncture, anticoagulated with heparin, citrate or acid-citrate-dextrose (ACD) +\/- recalcification and stored for 30-120 min before stimulation at room temperature or 37\u00b0C with adenosine diphosphate (ADP), cross-linked collagen-related peptide (CRP-XL) and protease-activated receptor 4-activating peptide (PAR4-AP). PLA formation and leukocyte activation were analyzed by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Basal PLAs were minimally affected by blood sampling and anticoagulant, though delayed processing significantly raised basal PLAs. Agonist-induced PLA formation was independent of anticoagulation, and sampling technique did not affect ADP- or PAR4-AP-induced PLA levels. However, CRP-XL sensitivity was elevated in blood obtained by cardiac puncture. Contrarily, both delayed processing and stimulation at 37\u00b0C impaired CRP-XL sensitivity, but augmented ADP and PAR4-AP responses. Regulation of leukocyte activation did not follow PLA patterns, with monocytes and neutrophils displaying distinct susceptibility to anticoagulation, storage and temperature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Variations in preparing murine blood samples exert distinct influences on platelet-leukocyte interactions <jats:italic>in vitro<\/jats:italic>, underlining the critical need for fastidious assay optimization to support data reproducibility and comparability.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1637038","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T12:32:22Z","timestamp":1756816342000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Experimental conditions shape in vitro formation of murine platelet-leukocyte aggregates"],"prefix":"10.3389","volume":"16","author":[{"given":"Silvia Maria 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