Lysosome-induced Increase in Intracellular Granularity of Leukocytes: a Key Morphological Biomarker for Early Sepsis in Cell Population Data

Early and rapid identification of sepsis is critical for improving clinical outcomes; however, reliable real-time biomarkers remain unavailable. The scattergram parameters of peripheral blood circulating leukocytes are altered during infection and sepsis. This study aims to explore the cellular biological characteristics underlying these changes, with a particular focus on morphological complexity. An in vitro human whole-blood infection model was constructed by stimulating isolated healthy human peripheral blood with lipopolysaccharide (LPS). Concurrently, a sepsis mouse model was established via intraperitoneal LPS injection. Subsequently, protein kinase C and myeloid differentiation primary-response protein 88 (MyD88) inhibitors were administered separately to establish corresponding inhibition models in mice. The total lysosomal contents in leukocytes and monocytes were then detected to analyze the intrinsic mechanism responsible for the sepsis-associated changes in the scattergram parameters. The results indicated elevated lysosome counts in leukocytes raised N_WBC_SFL_W, whereas those in monocytes drove higher D_Mon_SSC_W under septic conditions. This study reveals that the increased lysosomal content is the primary cause of the heightened number of cytoplasmic granules in leukocytes during sepsis. Furthermore, it clarifies that the characteristic changes in the scattergram parameters N_WBC_SFL_W and D_Mon_SSC_W detected through hematological analysis are a consequence of alterations in the lysosomal content. Collectively, our finding demonstrates that sepsis-induced alterations in leukocytes are hematological manifestations of aberrant lysosomal expansion, providing novel mechanistic insights for sepsis diagnosis and potential therapeutic monitoring.