Novel interactions between erythroblast macrophage protein and cell migration

Abstract

Erythroblast macrophage protein is a novel protein known to mediate attachment of erythroid cells to macrophages to form erythroblastic islands in bone marrow during erythropoiesis. Emp-null macrophages are small with round morphologies, and lack cytoplasmic projections which imply immature structure. The role of Emp in macrophage development and function is not fully elucidated. Macrophages perform varied functions (e.g. homeostasis, erythropoiesis), and are implicated in numerous pathophysiological conditions such as cellular malignancy. The objective of the current study is to investigate the interaction of Emp with cytoskeletal- and cell migration-associated proteins involved in macrophage functions. A short hairpin RNA lentiviral system was use to down-regulate the expression of Emp in macrophage cells. A cell migration assay revealed that the relocation of macrophages was significantly inhibited when Emp expression was decreased. To further analyze changes in gene expression related to cell motility, PCR array was performed by down-regulating Emp expression. The results indicated that expression of mitogen-activated protein kinase 1 and thymoma viral proto-oncogene 1 were significantly higher when Emp was down-regulated. The results implicate Emp in abnormal cell motility, thus, warrants to assess its role in cancer where tumor cell motility is required for invasion and metastasis.

An Overview of Different Strategies to Recreate the Physiological Environment in Experimental Erythropoiesis

“…Specific interactions have been identified to play a key role in the formation and integrity of this organization: integrin-α4β1 binding/vascular adhesion molecule-1(VCAM-1), intercellular adhesion molecule-4 (ICAM-4)/integrin-αV, and erythroblast macrophage protein (EMP) or macrophage erythroblast attacher (MAEA) ( Figure 1 ), present on both cells [ 90 , 91 , 92 , 93 , 94 , 95 ]. Moreover, EMP/MAEM binding could be involved in EBI migration due to the presumed involvement of EMP in the Erk1/Erk2 or PI3/Akt pathways as well as the regulation of gene expression associated with cell motility [ 96 , 97 ]. Furthermore, erythroblast/macrophage interaction appears to be a complex process that involves several more molecules than those described today.…”

Differential tissue expression of erythroblast macrophage protein in a MRL/lpr mouse model of lupus

“…In contrast, autoimmune hepatitis is one of the major organ impairments of lupus erythematosus. When Javan et al lowered the EMP expression of macrophages via an EMP-shRNA lentivirus system, 11 the macrophage movement was obviously controlled, confirming that abnormal EMP function can influence the function of macrophages. Cell locomotion is a dynamic process with favorable coordination.…”

“…First discovered by Hanspal and Hanspal, it is expressed on the surface of macrophages and normoblasts in the center of hematopoietic island of bone marrow. 7 It is secreted by normoblasts and macrophages, [8][9][10][11] and is a key protein that induces normoblast denucleation and maturation. [12][13][14] Normoblasts produce a complete solitary nucleus during the denucleation process, which occurs without other cellular components.…”

Erythroblast macrophage protein (Emp): Past, present, and future

“…[57][58][59][60] Recently, a study analyzed transcriptional responses of cell motility-related genes, when Emp is under expressed. 61 GIPZ lentiviral shRNA gene silencing system was utilized to reduce the expression of Emp and to evaluate the protein's affect on cell motility. Results showed that cellular migration was significantly impaired when Emp was downregulated in macrophages.…”

“…Recently, a study analyzed transcriptional responses of cell motility‐related genes, when Emp is under expressed . GIPZ lentiviral shRNA gene silencing system was utilized to reduce the expression of Emp and to evaluate the protein's affect on cell motility.…”