Analysis of Subendothelial Leukocyte Infiltration in the Trabecular Veins of Septic Spleen

Abstract

The splenic white pulp (WP) consists of CD20-positive lymph follicles (LFs) and CD3-positive periarteriolar lymphoid sheaths. Atrophy of the WP associated with a prolonged period of sepsis is a well-known pathological finding at autopsy. On the other hand, dense subendothelial leukocyte infiltration in the trabecular veins is also commonly observed in autopsy specimens of septic spleen. However, the characteristics and significance of this finding have not yet been well studied. In this study, autopsy spleens obtained from 55 sepsis and 45 non-sepsis patients were compared to determine the clinicopathological characteristics of subendothelial leukocyte infiltration in the trabecular veins, and its pathological significance was discussed. Severe and mild subendothelial leukocyte infiltration in the trabecular veins was observed in 45.5% of sepsis patients, but was absent in non-sepsis patients. Several clinicopathological characteristics of subendothelial leukocyte infiltration were identified. Firstly, the majority of infiltrated cells were lymphocytes. Secondly, both incidence and degree of infiltration were decreased at the late phase of sepsis accompanied by atrophy of the WP. Thirdly, types and compositions of infiltrated leukocytes reflected the histological findings of the spleen. Thus, the percentage of CD20-positive cells in the infiltrating cells into the subendothelium was proportional to the relative size of the CD20-positive area in the specimen, and the percentage of MUM1-p-positive cells in the infiltrating cells was proportional to the frequency of appearance of MUM1-p-positive cells in the red pulp. The CD20-positive area approximated the relative size of the WP in the septic cases, while the frequency of appearance of MUM1-p-positive cells was indicative of the differentiation levels of LFs into plasma cells upon antigen stimulation. Lastly, the intense subendothelial infiltration of CD20-positive cells was specific for the early stage of sepsis, and the morphological characteristics of these CD20-positive cells suggested their association with the marginal zone. Based on these clinicopathological characteristics and the fact that leukocyte infiltration into the subendothelium of trabecular veins became undetectable as atrophy of the WP progressed, it was suggested that the infiltrating cells had migrated from the WP, and this cell infiltration is an early activated immunological reaction in the spleen. Furthermore, the presence of possible efflux or drainage routes in the subendothelial spaces of trabecular veins was suggested.