Red pulp macrophages in the human spleen are a distinct cell population with a unique expression of Fc-? receptors.

ABSTRACT: Tissue-resident macrophages in the spleen play a major role in the clearance of immunoglobulin G (IgG)-opsonized blood cells, as occurs in immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Blood cells are phagocytosed via the Fc-? receptors (Fc?Rs), but little is known about the Fc?R expression on splenic red pulp macrophages in humans, with only a few previous studies that showed conflicting results. We developed a novel method to specifically isolate red pulp macrophages from 82 human spleens. Surface expression of various receptors and phagocytic capacity was analyzed by flow cytometry and immunofluorescence of tissue sections. Red pulp macrophages were distinct from splenic monocytes and blood monocyte-derived macrophages on various surface markers. Human red pulp macrophages predominantly expressed the low-affinity receptors Fc?RIIa and Fc?RIIIa. In contrast to blood monocyte-derived macrophages, red pulp macrophages did not express the inhibitory Fc?RIIb. Red pulp macrophages expressed very low levels of the high-affinity receptor Fc?RI. Messenger RNA transcript analysis confirmed this expression pattern. Unexpectedly and despite these differences in Fc?R expression, phagocytosis of IgG-opsonized blood cells by red pulp macrophages was dependent on the same Fc?Rs as phagocytosis by blood monocyte-derived macrophages, especially in regarding the response to IV immunoglobulin. Concluding, we show the distinct nature of splenic red pulp macrophages in human subjects. Knowledge on the Fc?R expression and usage of these cells is important for understanding and improving treatment strategies for autoimmune diseases such as ITP and AIHA.

SUBMITTER: Nagelkerke SQ 

PROVIDER: S-EPMC5916003 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature