TY - JOUR
T1 - Expression and function of a CD4-like molecule in parathyroid tissue
AU - Hellman, P.
AU - Karlsson-Parra, A.
AU - Klareskog, L.
AU - Ridefelt, P.
AU - Bjerneroth, G.
AU - Rastad, J.
AU - Akerstrom, G.
AU - Juhlin, C.
AU - Brunt, L. M.
AU - McHenry, C. R.
N1 - Funding Information:
PARATHYROIDC ELLSI NTERACTi n the calcium homeostasis by altering the secretion of parathyroid hormone (PTH) in relation to the extracellular Ca 2§ concentration. This regulation involves sensing of extracellular Ca 2+, transduction of the signal into the parathyroid cells, intracellular Ca 2+ mobilization, and Ca 2+ influx through non-voltage-dependent channels. 1' 2 A recendy identified ~500 kd glycoprotein (CAS) on the parathyroid cell surface constitutes one putative Ca 2+ sensing molecule, which belongs to the low-density lipoprotein receptor superfamily. 3 Incubation with monoclonal antibodies to certain epitopes of this protein blocks the increase in cytoplasmic Ca 2+ concentration (\[Ca2 +\]i ) and the concomitant decrease in PTH secretion, which result from exposure of normal and patho- Supported by the Swedish Medical Research Council, the Swedish Cancer Society, and the Swedish Society of Physicians. Presented at the Seventeenth Annual Meeting of the American Association of Endocrine Surgeons, Napa, Calif., April 21-23, 1996. Reprint requests: Per Hellman, MD, Department of Surgery, University Hospital, S-751 85 Uppsala, Sweden. Copyright 9 1996 by Mosby-YearB ook, Inc. 0039-6060/96/$5.00+0 11/6/75774 logic parathyroid cells to increased extracellular Ca 2+ levels. 4 Parathyroid cells also express other molecules with potential functional effects. The CD3 complex of lymphocytes and an anti-CD4 immunoreactive protein have been shown on pathologic parathyroid cells. B, 6 Apart from these similarities, both parathyroid cells and lymphocytes exhibit non-voltage-dependent Ca 2+ permeability. 1'7 This study substantiates that normal and pathologic human parathyroid cells express a virtually T-cell identical CD4 moiety, which can interact in the regulation of PTH release. Functional relevance of this retroviral receptor in vivo was supported by the demonstration that individuals infected with human immunodeficiency virus type 1 (H1V1) exhibit lower serum PTH levels, possibly related to virus or anti-CD4 antibody interaction with the parathyroid parenchyma.
PY - 1996
Y1 - 1996
N2 - Background. Parathyroid tissue expresses the T-lymphocyte antigens CD3 and CD4, and parathyroid CD3 has earlier been proposed to interact in the regulation of parathyroid hormone (PTH) release. Methods. Anti-Leu3a, a monoclonal antibody recognizing CD4, was used to stain parathyroid tissue immunohistochemically, to influence PTH secretion from enzymatically dispersed parathyroid cells, and to immunoprecipitate parathyroid CD4. Northern blot and polymerase chain reaction were used to clarify the similarity between parathyroid and lymphocytic CD4. Serum PTH level was measured with an immunoradiometric assay in healthy control subjects and individuals with human immunodeficiency virus type 1. Results. The parenchyma of normal and abnormal parathyroid tissue displayed strikingly variable CD4 expression. Immunoprecipitation showed a 56 kd molecule, and Northern blot and polymerase chain reaction confirmed the similarity with lymphocyte CD4. Anti-Leu3a inhibited preferentially low calcium-stimulated secretion of PTH from dispersed parathyroid cells, without discernible influences on the cytoplasmic calcium concentration of these cells. Individuals with human immunodeficiency virus type 1 displayed significantly lower serum PTH levels than healthy control subjects. Conclusions: The results suggest that the human parathyroid chief cell expresses a CD4 moiety, which seems to interact in the PTH release in vitro and in vivo and which seems to use another second messenger system than the structurally similar T-cell equivalent.
AB - Background. Parathyroid tissue expresses the T-lymphocyte antigens CD3 and CD4, and parathyroid CD3 has earlier been proposed to interact in the regulation of parathyroid hormone (PTH) release. Methods. Anti-Leu3a, a monoclonal antibody recognizing CD4, was used to stain parathyroid tissue immunohistochemically, to influence PTH secretion from enzymatically dispersed parathyroid cells, and to immunoprecipitate parathyroid CD4. Northern blot and polymerase chain reaction were used to clarify the similarity between parathyroid and lymphocytic CD4. Serum PTH level was measured with an immunoradiometric assay in healthy control subjects and individuals with human immunodeficiency virus type 1. Results. The parenchyma of normal and abnormal parathyroid tissue displayed strikingly variable CD4 expression. Immunoprecipitation showed a 56 kd molecule, and Northern blot and polymerase chain reaction confirmed the similarity with lymphocyte CD4. Anti-Leu3a inhibited preferentially low calcium-stimulated secretion of PTH from dispersed parathyroid cells, without discernible influences on the cytoplasmic calcium concentration of these cells. Individuals with human immunodeficiency virus type 1 displayed significantly lower serum PTH levels than healthy control subjects. Conclusions: The results suggest that the human parathyroid chief cell expresses a CD4 moiety, which seems to interact in the PTH release in vitro and in vivo and which seems to use another second messenger system than the structurally similar T-cell equivalent.
UR - http://www.scopus.com/inward/record.url?scp=0029907081&partnerID=8YFLogxK
U2 - 10.1016/S0039-6060(96)80044-4
DO - 10.1016/S0039-6060(96)80044-4
M3 - Article
C2 - 8957484
AN - SCOPUS:0029907081
SN - 0039-6060
VL - 120
SP - 985
EP - 992
JO - Surgery
JF - Surgery
IS - 6
ER -