Matrix metalloproteinase and tissue inhibitor of metalloproteinase in human bone marrow tissues-an immunohistochemical study

Unlike other tissues, bone marrow (BM) seldom displays fibrosis after injury, suggesting a possible suppressive mechanism against secondary myelofibrosis in BM tissues. We investigated if fibrosis-related factors, such as matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP), were expressed in BM tissues in vivo. We attempted immunohistochemical studies on specimens of 16 BM aspiration materials with normal hematological findings and 21 BM tissues from autopsy cases who had succumbed to acute heart failure or cerebrovascular diseases without any BM injuries. Identification of immunohistochemically reactive MMP-2, MMP-9 and TIMP-2 in BM tissue samples revealed for the first time that MMP-2 was localized in the myeloid cells, erythroblasts and megakaryocytes, MMP-9 in the myeloid cells and megakaryocytes. In addition, expression of TIMP-2 in the megakaryocytes as well as in the histiocytes within the stroma was verified. In the non-pathological condition, MMP/TIMP expressions were not encountered in BM stromal cells, such as fibroblasts, vascular endothelial cells, reticulum cells on adipocytes, except for TIMP-2 identification in stromal histiocytes. It is highly possible that these MMP and TIMP expressions in the BM hematopoietic cells and stromal histiocytes are significantly associated with suppression or induction of myelofibrosis.