A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease

• DOI: 10.1371/journal.pcbi.1011223
• Publication Date: 2023-12-13T18:38:38Z
• Authors: Guansheng Li; Yuhao Qiang; He Li; Xuejin Li; Pierre A. Buffet; Ming Dao; George Em Karniad...
• Keywords: Red pulp

Being the largest lymphatic organ in body, spleen also constantly controls quality of red blood cells (RBCs) circulation through its two major filtration components, namely interendothelial slits (IES) and pulp macrophages. In contrast to extensive studies understanding function IES, fewer works investigate how splenic macrophages retain aged diseased RBCs, i.e., RBCs sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments quantify dynamics captured retained We first calibrate parameters model based on microfluidic experimental measurements for under normoxia hypoxia, as those are not available literature. Next, impact key factors expected dictate RBC retention spleen, namely, flow conditions, aggregation, hematocrit, morphology, oxygen levels. Our simulation results show that hypoxic conditions could enhance adhesion between This, turn, increases much four-fold, which be possible cause congestion patients with SCD. aggregation illustrates 'clustering effect', where multiple one aggregate can make contact adhere macrophages, leading higher rate than resulting from RBC-macrophage pair interactions. simulations flowing past range velocities indicate increased velocity quickly attenuate detaining or thereby providing rationale slow open spleen. Furthermore, morphology their tendency find granular-shaped more likely filtered This finding is consistent observation low percentages these forms smear SCD patients. Taken together, our aid quantitative retaining provide an opportunity combine such knowledge current interaction IES traversing apprehend complete