Immunosuppressive Effects of Corticotropin and Melanotropin and Their Possible Significance in Human Immunodeficiency Virus Infection

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Jan 25

PMID 1309958

Citations 7

Authors

E M Smith

T K Hughes Jr

F Hashemi

G B Stefano

Affiliations

Soon will be listed here.

Abstract

The activation of human granulocytes and invertebrate immunocytes was found to be suppressed by corticotropin (ACTH) and melanotropin (MSH). In spontaneously active granulocytes both neuropeptides caused significant conformational changes indicative of inactivity plus a reduction in their locomotion. Significant inactivation of human granulocytes by ACTH required 2 hr, that by MSH only 20 min. The addition to the incubation medium of phosphoramidon, a specific inhibitor of neutral endopeptidase 24.11, blocked inactivation of granulocytes by ACTH. Radioimmunoassay for MSH of supernatant fluids from granulocytes incubated with ACTH demonstrated a time-dependent increase in MSH. These data strongly indicate that the effect of ACTH is largely due to its conversion to MSH by granulocyte-associated neutral endopeptidase. Parallel experiments with immunocytes from the mollusc Mytilus edulis gave similar results, indicating the universality of this phenomenon. Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections.

Citing Articles

Opioid peptides and opiate alkaloids in immunoregulatory processes.

Stefano G, Kream R Arch Med Sci. 2012; 6(3):456-60.

PMID: 22371785 PMC: 3282526. DOI: 10.5114/aoms.2010.14271.

Neuropeptides as signal molecules in common with leukocytes and the hypothalamic-pituitary-adrenal axis.

Smith E Brain Behav Immun. 2007; 22(1):3-14.

PMID: 17900859 PMC: 2194290. DOI: 10.1016/j.bbi.2007.08.005.

Further structure-activity studies of lactam derivatives of MT-II and SHU-9119: their activity and selectivity at human melanocortin receptors 3, 4, and 5.

Grieco P, Cai M, Han G, Trivedi D, Campiglia P, Novellino E Peptides. 2007; 28(6):1191-6.

PMID: 17482720 PMC: 1955225. DOI: 10.1016/j.peptides.2007.02.012.

ACTH enhancement of T-lymphocyte cytotoxic responses.

Johnson E, Hughes Jr T, Smith E Cell Mol Neurobiol. 2005; 25(3-4):743-57.

PMID: 16075388 PMC: 11529561. DOI: 10.1007/s10571-005-3972-8.

Mechanism of action of melanocortin peptides. Possible role in astrocyte regulation.

Zohar M, Salomon Y J Mol Neurosci. 1993; 4(1):55-62.

PMID: 8391297 DOI: 10.1007/BF02736690.

References

Kavelaars A, Ballieux R, Heijnen C . Modulation of the immune response by proopiomelanocortin derived peptides. II. Influence of adrenocorticotropic hormone on the rise in intracellular free calcium concentration after T cell activation. Brain Behav Immun. 1988; 2(1):57-66. DOI: 10.1016/0889-1591(88)90006-2. View

Cushman D, Cheung H, SABO E, ONDETTI M . Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry. 1977; 16(25):5484-91. DOI: 10.1021/bi00644a014. View

Deschodt-Lanckman M, Vanneste Y, Loir B, Michel A, Libert A, Ghanem G . Degradation of alpha-melanocyte stimulating hormone (alpha-MSH) by CALLA/endopeptidase 24.11 expressed by human melanoma cells in culture. Int J Cancer. 1990; 46(6):1124-30. DOI: 10.1002/ijc.2910460629. View

Bost K, Clarke B, Xu J, Kiyono H, McGhee J, Pascual D . Modulation of IgM secretion and H chain mRNA expression in CH12.LX.C4.5F5 B cells by adrenocorticotropic hormone. J Immunol. 1990; 145(12):4326-31. View

Lipton J . Modulation of host defense by the neuropeptide alpha-MSH. Yale J Biol Med. 1990; 63(2):173-82. PMC: 2589306. View

Stefano G, Leung M, Zhao X, Scharrer B . Evidence for the involvement of opioid neuropeptides in the adherence and migration of immunocompetent invertebrate hemocytes. Proc Natl Acad Sci U S A. 1989; 86(2):626-30. PMC: 286525. DOI: 10.1073/pnas.86.2.626. View

Clarke B, Bost K . Differential expression of functional adrenocorticotropic hormone receptors by subpopulations of lymphocytes. J Immunol. 1989; 143(2):464-9. View

Stefano G, Cadet P, Scharrer B . Stimulatory effects of opioid neuropeptides on locomotory activity and conformational changes in invertebrate and human immunocytes: evidence for a subtype of delta receptor. Proc Natl Acad Sci U S A. 1989; 86(16):6307-11. PMC: 297827. DOI: 10.1073/pnas.86.16.6307. View

Koff W, Dunegan M . Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones. J Immunol. 1985; 135(1):350-4. View

10.

Smith E, Brosnan P, Meyer W, Blalock J . An ACTH receptor on human mononuclear leukocytes. Relation to adrenal ACTH-receptor activity. N Engl J Med. 1987; 317(20):1266-9. DOI: 10.1056/NEJM198711123172006. View

11.

Harbour D, Smith E, Blalock J . Novel processing pathway for proopiomelanocortin in lymphocytes: endotoxin induction of a new prohormone-cleaving enzyme. J Neurosci Res. 1987; 18(1):95-101. DOI: 10.1002/jnr.490180116. View

12.

Johnson E, Blalock J, Smith E . ACTH receptor-mediated induction of leukocyte cyclic AMP. Biochem Biophys Res Commun. 1988; 157(3):1205-11. DOI: 10.1016/s0006-291x(88)81002-7. View

13.

Turner A, Matsas R, Kenny A . Are there neuropeptide-specific peptidases?. Biochem Pharmacol. 1985; 34(9):1347-56. DOI: 10.1016/0006-2952(85)90669-0. View

14.

Harper M, Marselle L, Gallo R, Wong-Staal F . Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986; 83(3):772-6. PMC: 322947. DOI: 10.1073/pnas.83.3.772. View

15.

Smith E . Hormonal activities of lymphokines, monokines, and other cytokines. Prog Allergy. 1988; 43:121-39. DOI: 10.1159/000318732. View

16.

Duesberg P . HIV is not the cause of AIDS. Science. 1988; 241(4865):514, 517. DOI: 10.1126/science.3399880. View

17.

Scott A, Ratcliffe J, Rees L, LANDON J, Bennett H, Lowry P . Pituitary peptide. Nat New Biol. 1973; 244(133):65-7. DOI: 10.1038/newbio244065a0. View

18.

Smith E, Blalock J . Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon. Proc Natl Acad Sci U S A. 1981; 78(12):7530-4. PMC: 349302. DOI: 10.1073/pnas.78.12.7530. View

19.

Johnson H, Smith E, Torres B, Blalock J . Regulation of the in vitro antibody response by neuroendocrine hormones. Proc Natl Acad Sci U S A. 1982; 79(13):4171-4. PMC: 346599. DOI: 10.1073/pnas.79.13.4171. View

20.

Sayers G, Seelig S, Kumar S . Isolated adrenal cortex cells in suspension: stimulation and inhibition of steroidogenesis by analogues of ACTH. J Steroid Biochem. 1975; 6(3-4):371-5. DOI: 10.1016/0022-4731(75)90159-4. View