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sHLH in LPS-treated SAMP/TA-1 mice
proportions of M1 and M2 macrophages in SAMR1 and SAMP1/TA-1 mice after the first LPS treatment. The pro- portion of M2 macrophages (CD11b+/CD206+ cells) was higher than that of M1 macrophages (CD11b+/iNOS+ cells) in both non-treated SAMR1 and non-treated SAMP1/TA- 1 mice. When treated with LPS, the proportions of M1 macrophages in SAMR1 and SAMP1/TA-1 mice were increased by day 2. Thereafter, although the proportions of M1 macrophages decreased in both SAMR1 and SAMP1/TA-1 mice, the magnitude of the decrease in the proportions of M1 macrophages on day 5 after LPS treat- ment differed between SAMR1 and SAMP1/TA-1 mice. Namely, the proportion of M1 macrophages in SAMP1/TA-1 mice remained high (8.0% of M1 cells) com- pared with that in SAMR1 mice (1.4% of M1 cells).
When treated with LPS, the proportions of M2 macrophages remained unchanged in both SAMR1 and SAMP1/TA-1 mice by day 2. Thereafter, the proportion of M2 macrophages in SAMP1/TA-1 mice decreased by day 5 (52.5% to 30.2%), whereas the proportion of M2 macrophages in SAMR1 mice remained high (57.2% to 58.4%).
Discussion
Several murine models of primary HLH and sHLH have been described. Murine models of primary HLH were gen- erated by deletion of perforin and Rab27a genes, and mutation of the Unc13d gene, leading to defects in the granule exocytic pathway.28-30 In contrast, sHLH can be induced by Epstein-Barr virus infection in humanized mice transplanted with human CD34+ cells, Salmonella enteritica infection in Sv12956 mice, and cytomegalovirus infection in BALB/c mice.25,31,32 Furthermore, C57BL/6 mice repeatedly given the toll-like receptor 9 agonist, CpG, and IL-6 transgenic mice given LPS also develop sHLH.33,34
Henter et al.1 proposed that the diagnosis of HLH is based on eight criteria, including fever, splenomegaly bicytopenia, hypertriglyceremia and/or hypofibriogene- mia, hemophagocytosis, low/absent natural killer-cell activity, hyperferritinemia, and high levels of soluble IL-2 receptor. Five of these eight criteria must be fulfilled for a diagnosis, unless a family history is present that is consis- tent with sHLH. When repeatedly treated with LPS, SAMP1/TA-1 mice showed hepatosplenomegaly, pancy-
AB
CD
Figure 6. Numerical changes in hematopoietic progenitor cells in the bone marrow from SAMR1 and SAMP1/TA-1 mice after lipopolysaccharide treatment. (A-D) The numbers of hematopoietic progenitor cells in the femoral bone marrow of SAMR1 and SAMP1/TA-1 mice after repeated treatment with lipopolysaccharide (LPS) are shown: myeloid progenitors, CFU-GM (A); B lymphoid progenitors, CFU-preB (B); erythroid progenitors, BFU-E (C); and megakaryocytic progenitors, CFU-Mk (D). The samples of femoral bone marrow cells were obtained from non-treated control mice (day 0) and mice 7, 14, and 21 days after the first treatment with 25 μg LPS. Each bar represents the mean ± standard deviation obtained from three mice. *P<0.05, †P<0.005 vs. non-treated control.
haematologica | 2019; 104(10)
2001