title: Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line.
abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34(+)CD41a(+) and CD41a(+)CD42b(+) cells. LAIR-1 is also detectable in a fraction of human cord blood CD34(+) cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34(+) cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai, China. xuejinagnan@263.net
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Xue
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Zhang
authors.forename: Haiya
authors.initials: H
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Yanning
authors.initials: Y
authors.lastname: Cao
authors.forename: Yuesi
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Feng
authors.forename: Aili
authors.initials: A
authors.lastname: Fu
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D002460:Cell Line; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D040201:Platelet Membrane Glycoprotein IIb; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; D013755:Tetradecanoylphorbol Acetate