title: Expression of the L1 antigen (calprotectin) by tissue macrophages reflects recent recruitment from peripheral blood rather than upregulation of local synthesis: implications for rejection diagnosis in formalin-fixed kidney specimens.
abstract: The L1 antigen (calprotectin) is present in circulating monocytes but is restricted to certain subsets of tissue macrophages. Its expression is significantly increased in inflammatory bowel disease, apparently because of newly recruited monocytes. In vitro experiments were performed to substantiate lack of L1 upregulation in tissue macrophages, thereby justifying the use of this marker to detect newly recruited cells. Its reliability was further evaluated by studying mononuclear cell infiltrates characteristic of acute kidney rejection. After pro-inflammatory stimulation, monocytes matured in vitro (n = 12) as well as adherent mononuclear cells from normal small intestinal mucosa (n = 5) were examined for L1 expression by immunocytochemistry and by ELISA (cell lysates). In addition, peritubular mononuclear L1+ cells were examined by immunohistochemistry in routine biopsy specimens from transplanted kidneys with (n = 11) or without (n = 14) histopathologically diagnosed acute rejection. L1 was not upregulated in monocytes matured in vitro, nor in mucosal macrophages after stimulation with interferon-gamma, LPS, phorbol ester, or supernatant from activated leucocytes. In transplanted kidneys with signs of acute rejection, the fraction of L1+ macrophages was significantly increased (P < 0.001). Because L1 is persistently downregulated in mature tissue macrophages and is formalin-resistant, it identifies young infiltrating macrophages in routinely processed biopsy material. L1 should therefore be a valuable adjunct in the diagnosis of kidney rejection.
authors.affiliation: LIIPAT, Institute of Pathology, University of Oslo, The National Hospital, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Rugtveit
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.forename: T S
authors.initials: TS
authors.lastname: Halstensen
authors.forename: J
authors.initials: J
authors.lastname: Norstein
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
mesh_terms: D001706:Biopsy; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D039841:Leukocyte L1 Antigen Complex; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*
chemical_list: D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules