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Brief Report: Alternative Activation of Laser‐Captured Murine Hemophagocytes
Author(s) -
Canna Scott W.,
CostaReis Patrícia,
Bernal William E.,
Chu Niansheng,
Sullivan Kathleen E.,
Paessler Michele E.,
Behrens Edward M.
Publication year - 2014
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38379
Subject(s) - cd163 , cd64 , bone marrow , laser capture microdissection , haematopoiesis , hemophagocytosis , macrophage , pathology , hemophagocytic lymphohistiocytosis , immunohistochemistry , cd68 , biology , macrophage activation syndrome , medicine , immunology , microbiology and biotechnology , gene expression , flow cytometry , gene , stem cell , biochemistry , disease , pancytopenia , in vitro
Objective Hemophagocytes (HPCs) are activated macrophages that have engulfed other hematopoietic cells. Although HPCs are rarely identified in normal spleen tissue and bone marrow, an excess of these macrophages characterizes many cytokine storm syndromes, particularly macrophage activation syndrome and hemophagocytic lymphohistiocytosis. This study was undertaken to assess the functions of HPCs and their significance in acute inflammatory conditions. Methods HPCs were generated in wild‐type mice using repeated stimulation with Toll‐like receptor 9 (TLR‐9) and interleukin‐10 receptor blockade. RNA was extracted from HPCs that had been isolated by laser‐captured microdissection. Transcriptional profiles of the HPCs were then compared to those of resting splenic macrophages. In addition, bone marrow samples were obtained from a diverse cohort of patients in whom excess hemophagocytosis was identified by clinical bone marrow biopsy or aspiration. The bone marrow samples were analyzed by immunohistochemistry for markers of classic (CD64) or alternative (CD163 and CD206) macrophage activation. Results Differential gene expression and gene set enrichment analyses of murine HPCs identified up‐regulation of genes and gene sets associated with alternative activation of HPCs. Immunohistochemical analyses of HPCs in human bone marrow samples showed universal staining of HPCs for CD163, but rarely for CD206 or CD64. Conclusion Laser‐captured murine TLR‐9–induced HPCs had a transcriptional profile similar to that of alternatively activated macrophages. In addition, HPC expression of CD163 was confirmed in a uniquely diverse cohort of patients with hemophagocytic syndromes. Collectively, these data support the hypothesis that HPCs have both immunoregulatory and clean‐up functions.