Naive Human T Cells Are Activated and Proliferate in Response to the Heme Oxygenase-1 Inhibitor Tin Mesoporphyrin

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2010 Oct 6

PMID 20921523

Citations 25

Authors

Trevor D Burt

Lillian Seu

Jeffrey E Mold

Attallah Kappas

Joseph M McCune

Affiliations

Soon will be listed here.

Abstract

Heme oxygenase-1 (HO-1) and its catabolic by-products have potent anti-inflammatory activity in many models of disease. It is not known, however, if HO-1 also plays a role in the homeostatic control of T cell activation and proliferation. We demonstrate here that the HO-1 inhibitor tin mesoporphyrin (SnMP) induces activation, proliferation, and maturation of naive CD4(+) and CD8(+) T cells via interactions with CD14(+) monocytes in vitro. This response is dependent upon interactions of T cells with MHC class I and II on the surface of CD14(+) monocytes. Furthermore, CD4(+)CD25(+)FoxP3(+) regulatory T cells were able to suppress this proliferation, even though their suppressive activity was itself impaired by SnMP. Given the magnitude of the Ag-independent T cell response induced by SnMP, we speculate that HO-1 plays an important role in dampening nonspecific T cell activation. Based on these findings, we propose a potential role for HO-1 in the control of naive T cell homeostatic proliferation.

Citing Articles

Development of a Competitive Nutrient-Based T-Cell Immunotherapy Designed to Block the Adaptive Warburg Effect in Acute Myeloid Leukemia.

Cao H, Xiao J, Baylink D, Nguyen V, Shim N, Lee J Biomedicines. 2024; 12(10).

PMID: 39457563 PMC: 11504511. DOI: 10.3390/biomedicines12102250.

The heme oxygenase-1 metalloporphyrin inhibitor stannsoporfin enhances the bactericidal activity of a novel regimen for multidrug-resistant tuberculosis in a murine model.

Castillo J, Neupane P, Karanika S, Krug S, Quijada D, Garcia A Antimicrob Agents Chemother. 2023; 68(2):e0104323.

PMID: 38132181 PMC: 10848751. DOI: 10.1128/aac.01043-23.

A glance through the effects of CD4 T cells, CD8 T cells, and cytokines on Alzheimer's disease.

Afsar A, Chen M, Xuan Z, Zhang L Comput Struct Biotechnol J. 2023; 21:5662-5675.

PMID: 38053545 PMC: 10694609. DOI: 10.1016/j.csbj.2023.10.058.

The heme oxygenase-1 metalloporphyrin inhibitor stannsoporfin enhances the bactericidal activity of a novel regimen for multidrug-resistant tuberculosis in a murine model.

Castillo J, Neupane P, Karanika S, Krug S, Quijada D, Garcia A bioRxiv. 2023; .

PMID: 37609351 PMC: 10441415. DOI: 10.1101/2023.08.09.552716.

Heme: The Lord of the Iron Ring.

Voltarelli V, Alves de Souza R, Miyauchi K, Hauser C, Otterbein L Antioxidants (Basel). 2023; 12(5).

PMID: 37237940 PMC: 10215292. DOI: 10.3390/antiox12051074.

References

Zhen Y, Zheng J, Zhao Y . Regulatory CD4+CD25+ T cells and macrophages: communication between two regulators of effector T cells. Inflamm Res. 2008; 57(12):564-70. DOI: 10.1007/s00011-008-7234-3. View

Kawashima A, Oda Y, Yachie A, Koizumi S, Nakanishi I . Heme oxygenase-1 deficiency: the first autopsy case. Hum Pathol. 2002; 33(1):125-30. DOI: 10.1053/hupa.2002.30217. View

Tan J, Dudl E, Leroy E, Murray R, Sprent J, Weinberg K . IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A. 2001; 98(15):8732-7. PMC: 37504. DOI: 10.1073/pnas.161126098. View

Sakaguchi S, Yamaguchi T, Nomura T, Ono M . Regulatory T cells and immune tolerance. Cell. 2008; 133(5):775-87. DOI: 10.1016/j.cell.2008.05.009. View

Poss K, Tonegawa S . Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci U S A. 1997; 94(20):10919-24. PMC: 23531. DOI: 10.1073/pnas.94.20.10919. View

Kim H, So H, Lee J, Lee J, Park C, Park S . Heme oxygenase-1 attenuates the cisplatin-induced apoptosis of auditory cells via down-regulation of reactive oxygen species generation. Free Radic Biol Med. 2006; 40(10):1810-9. DOI: 10.1016/j.freeradbiomed.2006.01.018. View

Lutton J, Jiang S, Drummond G, Abraham N, Kappas A . Comparative pharmacology of zinc mesoporphyrin and tin mesoporphyrin: toxic actions of zinc mesoporphyrin on hematopoiesis and progenitor cell mobilization. Pharmacology. 1998; 58(1):44-50. DOI: 10.1159/000028267. View

Ryter S, Alam J, Choi A . Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006; 86(2):583-650. DOI: 10.1152/physrev.00011.2005. View

Keyse S, Tyrrell R . Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A. 1989; 86(1):99-103. PMC: 286411. DOI: 10.1073/pnas.86.1.99. View

10.

Song R, Mahidhara R, Zhou Z, Hoffman R, Seol D, Flavell R . Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J Immunol. 2004; 172(2):1220-6. DOI: 10.4049/jimmunol.172.2.1220. View

11.

Otterbein L, Soares M, Yamashita K, Bach F . Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 2003; 24(8):449-55. DOI: 10.1016/s1471-4906(03)00181-9. View

12.

Remy S, Blancou P, Tesson L, Tardif V, Brion R, Royer P . Carbon monoxide inhibits TLR-induced dendritic cell immunogenicity. J Immunol. 2009; 182(4):1877-84. DOI: 10.4049/jimmunol.0802436. View

13.

George J, Braun A, Brusko T, Joseph R, Bolisetty S, Wasserfall C . Suppression by CD4+CD25+ regulatory T cells is dependent on expression of heme oxygenase-1 in antigen-presenting cells. Am J Pathol. 2008; 173(1):154-60. PMC: 2438293. DOI: 10.2353/ajpath.2008.070963. View

14.

Pae H, Oh G, Choi B, Chae S, Kim Y, Chung K . Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J Immunol. 2004; 172(8):4744-51. DOI: 10.4049/jimmunol.172.8.4744. View

15.

Lee P, Camhi S, Chin B, Alam J, Choi A . AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1. Am J Physiol Lung Cell Mol Physiol. 2000; 279(1):L175-82. DOI: 10.1152/ajplung.2000.279.1.L175. View

16.

Sato K, Balla J, Otterbein L, Smith R, Brouard S, Lin Y . Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol. 2001; 166(6):4185-94. DOI: 10.4049/jimmunol.166.6.4185. View

17.

Poss K, Tonegawa S . Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci U S A. 1997; 94(20):10925-30. PMC: 23533. DOI: 10.1073/pnas.94.20.10925. View

18.

Drummond G, Galbraith R, Sardana M, Kappas A . Reduction of the C2 and C4 vinyl groups of Sn-protoporphyrin to form Sn-mesoporphyrin markedly enhances the ability of the metalloporphyrin to inhibit in vivo heme catabolism. Arch Biochem Biophys. 1987; 255(1):64-74. DOI: 10.1016/0003-9861(87)90294-3. View

19.

Li M, Peterson S, Husney D, Inaba M, Guo K, Kappas A . Long-lasting expression of HO-1 delays progression of type I diabetes in NOD mice. Cell Cycle. 2007; 6(5):567-71. DOI: 10.4161/cc.6.5.3917. View

20.

Wyse C, Nixon C, Mclaughlin M, Dowell F, Philbey A . Evidence for the expression and enzymatic activity of haem oxygenase-1 in the lungs of horses. Vet Rec. 2006; 158(23):795-7. DOI: 10.1136/vr.158.23.795. View