Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
CELLULAR MECHANISMS OF LYMPHOCYTE-MEDIATED BONE RESORPTION
Diss Abstr Int [B]; 52(11):5768 1992. Unique Identifier : AIDSLINE ICDB/92686180 McCauley LK; Ohio State Univ.
Abstract:
Cells of the immune system have been reported to perform important regulatory functions in bone metabolism. The purpose of these studies was to gain a better understanding of the cellular mechanisms associated with cytokines, such as interleukin-1 (IL-1) and parathyroid hormone-related protein (PTHrP), and immunomodulators, such as cyclosporin A (CsA), and their involvement with bone remodeling. The effects of IL-1d and the ability of CsA to modify IL-1 alpha-induced effects were evaluated in mice. IL-1 alpha stimulated hypercalcemia, osteoclastic bone resorption, loss of trabecular bone, anorexia, neutrophilia and vascular thrombosis. Bone resorption stimulated by IL-1 alpha in vitro was inhibited by CsA; however, CsA did not markedly alter IL-1 alpha effects in vivo. Osteoblastlike cells were examined in vitro to determine if CsA effects on bone may be due to a direct action on the osteoblast. There was a significant inhibition of cell proliferation, cell number, mitogenesis and alkaline phosphatase, in addition to morphologic changes and reduced cell attachment in CsA-treated osteoblastlike cells. PTHrP is a potent bone-resorptive cytokine recently isolated from tumors which cause hypercalcemia of malignancy. Lymphocytes infected with HTLV-I secrete PTHrP, which may be responsible for hypercalcemia and lytic bone lesions in patients with HTLV-I-induced leukemia. An HTLV-I-infected cell line (MT-2) was evaluated for the presence of PTHrP receptors and biologic responses to PTHrP. High-affinity binding of PTHrP to MT-2 cells indicated the presence of specific receptors for PTHrP. PTHrP inhibited proliferation and increased intracellular calcium levels in MT-2 cells. Expression of PTHrP mRNA was evaluated by polymerase chain reaction amplification of MT-2 and MT-1 (low HTLV-I-virus-producing lymphocytes) cDNA. MT-2 and MT-1 cells expressed similar levels of PTHrP, indicating expression of PTHrP was not associated with viral antigen production. PTHrP expression was rapid and was stimulated by IL-2. In summary, cellular mechanisms of IL-1 alpha, CsA and PTHrP were evaluated. IL-1 alpha and CsA had profound effects on bone in vivo and in vitro. PTHrP was found to have a potential autocrine role in HTLV-I-infected lymphocytes, which provides insight to the bone-resorptive changes in patients with HTLV-I-induced leukemia. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD92-11177).
Keywords: Alkaline Phosphatase/METABOLISM Animal Bone Resorption/*IMMUNOLOGY Cell Adhesion Cell Division Cell Line Cyclosporine/PHARMACOLOGY HTLV-I Interleukin-1/PHYSIOLOGY Lymphocytes/CYTOLOGY/DRUG EFFECTS/*IMMUNOLOGY/MICROBIOLOGY Mice Osteoblasts/CYTOLOGY/DRUG EFFECTS Parathyroid Hormones/GENETICS/PHYSIOLOGY Polymerase Chain Reaction Proteins/GENETICS/PHYSIOLOGY Receptors, Cell Surface/METABOLISM RNA, Messenger/METABOLISM Substrate Specificity THESIS 921030
M92A1031
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
