Macrophage‐megakaryocyte interaction in bone marrow after high‐dose intravenous immunoglobulin therapy

Abstract

Localization of IgG in bone marrow after high-dose intravenous immunoglobulin therapy (IVIG) was investigated via light and electron microscopy. IgG was incorporated into the cytoplasm of various types of bone marrow cells of all the three lineages, particularly in reticulum cells, fat cells, and megakaryocytes. In addition, both reticulum cells and fat cells showed many elongated cytoplasmic protrusions, which were in contact with the various types of blood cells, especially the megakaryocytes. A filamentous structure was also seen near the point of contact between the cells. Ultrastructural changes of macrophages in bone marrow after IVIG suggest that these cells were activated by IVIG.

Cellular Contact between Red Blood Cell and Endothelial Cells after High Dose Immunoglobulin Therapy Might Depend on Non-Immunological Mechanism

“…The commercial human IgG product (Venoglogulin-I®, Green Cross Co., Japan) was used for the therapy in which the following components were contained in 1 ml; 50 mg of IgG, 10 mg of albumin, 5 mg of polyethylene glycol 4000, 20 mg of D-mannitol and 5 mg of sodium chloride. The morphological observation of megakaryocytes in BM after IVIG of one male or one female patient in this study had been previously reported [7].…”

“…We observed the direct cell-to cell contact between macrophages and megakaryocytes [7] by immuno-electron microscopy in BM of an ITP-patient after IVIG and have also found to adhesion between RBC and EC by chance. These pictures had never been observed at…”

“…Because the IgG was detected near the cytoplasmic surface of the ECs in humans after IVIG or in mice after human IgG injection, it showed that the IgG was incorporated into the ECs through its membrane [7]. Thus, it was expected that RBCs came to adhere firmly to the ECs through one of unique electric charge characteristics as the attraction of the positive and negative charges respectively.…”

M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity

“… 11 – 14 However, BM MΦs were reported to play both positive and negative roles in regulating megakaryopoiesis. 15 – 17 In patients with immune thrombocytopenia (ITP) who underwent intravenous immunoglobulin therapy, BM MΦs were found to closely contact MKs and were associated with increased platelet counts, suggesting that MΦs positively regulate megakaryopoiesis. 15 However, Alves-Rosa et al reported that depleting BM MΦs enhanced both megakaryopoiesis and platelet production in an ITP mouse model, which indicates that MΦs negatively regulate megakaryopoiesis.…”

“… 15 – 17 In patients with immune thrombocytopenia (ITP) who underwent intravenous immunoglobulin therapy, BM MΦs were found to closely contact MKs and were associated with increased platelet counts, suggesting that MΦs positively regulate megakaryopoiesis. 15 However, Alves-Rosa et al reported that depleting BM MΦs enhanced both megakaryopoiesis and platelet production in an ITP mouse model, which indicates that MΦs negatively regulate megakaryopoiesis. 16 , 17 Typically, MΦs can be polarized into classically activated (M1) MΦs and alternatively activated (M2) MΦs, with distinct phenotypic and unique functional characteristics.…”