Skip to main content

Advertisement

SpringerLink
Log in

Superoxide anion production by neutrophils is associated with prevalent clinical manifestations in systemic lupus erythematosus

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

To determine the relation between neutrophil function and the clinical characteristics of systemic lupus erythematosus (SLE), the superoxide anion (\({\text{O}}_2^ - \)) production by neutrophils, mediated by FcγR and FcγR/CR cooperation, was studied in 64 SLE patients classified according to their prevalent clinical manifestations. Three clinically distinct patterns were designated: (1) manifestations associated with the occurrence of cytotoxic antibodies (SLE-I group); (2) manifestations associated with circulating immune complexes (IC; SLE-II group), and (3) manifestations associated with IC and cytotoxic antibodies (SLE-III group). \({\text{O}}_2^ - \) production was evaluated by a lucigenin-dependent chemiluminescent assay in neutrophils stimulated with IC-IgG opsonized or not with complement. No difference in \({\text{O}}_2^ - \) production was observed when neutrophil responses from healthy controls were compared to the unclassified patients. However, when the SLE patient groups were considered, the following differences were observed: (1) SLE-I neutrophils showed lower \({\text{O}}_2^ - \) production mediated by the IgG receptor (FcγR) with the cooperation of complement receptors (FcγR/CR) than observed in the SLE-II, SLE-III, and healthy groups; (2) neutrophils from the SLE-II group showed a decreased \({\text{O}}_2^ - \) production mediated by FcγR/CR compared to the SLE-III group, (3) SLE-III neutrophils produced more \({\text{O}}_2^ - \) than neutrophils from the SLE-II and control groups, and (4) CR showed inefficiency in mediating the \({\text{O}}_2^ - \) production by neutrophils from the SLE-I group. Comparative experiments on the kinetics of chemiluminescence (CL; T max and CLmax) disclosed differences only for the SLE-I group. Taken together, these results suggest that differences in oxidative metabolism of neutrophils mediated by FcγR/CR may reflect an acquired characteristic of disease associated with distinct clinical manifestations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

aCL:

anticardiolipin

ACR:

American College of Rheumatology

ANA:

antinuclear antibodies

CLmax :

maximum rate of chemiluminescence

CFD:

complement fixation diluent

CR:

complement receptor

DEAE:

diethylaminoethyl

EDTA-:

ethylenediaminetetraacetate

FcγR:

Fc gamma receptor

HBSS:

Hanks’ balanced saline solution

IC:

immune complexes

INHS:

inactivated normal human serum

LAC:

lupus anticoagulant

NHS:

normal human serum

\({\text{O}}_2^ - \) :

superoxide anion

OVA:

ovalbumin

SEM:

standard error of the mean

SLE:

systemic lupus erythematosus

SLEDAI:

systemic lupus erythematosus disease activity index

T max :

time interval for the maximum rate of chemiluminescence

References

  1. Valko M, Leibfritz D, Moncol J et al (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84

    Article  PubMed  CAS  Google Scholar 

  2. Kurien BT, Hensley K, Bachmann M et al (2006) Oxidatively modified autoantigens in autoimmune diseases. Free Radic Biol Med 41:549–556

    Article  PubMed  CAS  Google Scholar 

  3. Alarcón-Segovia D, Alarcón-Riquelme ME (1999) Etiopathogenesis of Systemic Lupus Erythematosus: a tale of three troikas. In: Lahita RG (ed) Systemic lupus erythematosus. Academic, San Diego, CA, pp 55–65

    Google Scholar 

  4. Davies KA, Schifferli JA, Walport MJ (1994) Complement deficiency and immune complex disease. Springer Semin Immunopathol 15:397–416

    Article  PubMed  CAS  Google Scholar 

  5. Tsokos GC (1999) Overview of cellular immune functions in systemic lupus erythematosus. In: Lahita RG (ed) Systemic lupus erythematosus. Academic, San Diego, CA, pp 17–54

    Google Scholar 

  6. Ohara M, Shirado M, Miyata M et al (1983) Natural and antibody-dependent cellular cytotoxicity of polymorphonuclear leukocytes. Tohoku J Exp Med 140:59–66

    Article  PubMed  CAS  Google Scholar 

  7. Hebert LA (1991) The clearance of immune complexes from the circulation of man and other primates. Am J Kidney Dis 17:352–361

    PubMed  CAS  Google Scholar 

  8. Brown EJ (1992) Complement receptors, adhesion, and phagocytosis. Infect Agents Dis 1:63–70

    PubMed  CAS  Google Scholar 

  9. Colten HR, Rosen FS (1992) Complement deficiencies. Annu Rev Immunol 10:809–834

    Article  PubMed  CAS  Google Scholar 

  10. Van der Pol W, Van de Winkel JG (1998) IgG receptor polymorphisms: risk factors for disease. Immunogenetics 48:222–232

    Article  PubMed  Google Scholar 

  11. Iliopoulos AG, Tsokos GC (1996) Immunopathogenesis and spectrum of infections in systemic lupus erythematosus. Semin Arthritis Rheum 25:318–336

    Article  PubMed  CAS  Google Scholar 

  12. Hepburn AL, Mason JC, Wang S et al (2006) Both Fcg and complement receptors mediate transfer of immune complexes from erythrocytes to human macrophages under physiological flow conditions in vitro. Clin Exp Immunol 146:133–145

    Article  PubMed  CAS  Google Scholar 

  13. Szücs G, Kávai M, Kiss E et al (1995) Correlation of IgG Fc receptors on granulocytes with serum immune complex level in systemic lupus erythematosus. Scand J Immunol 42:577–580

    Article  PubMed  Google Scholar 

  14. Marzocchi-Machado CM, Alves CM, Azzolini AE et al (2002) Fcγ and complement receptors: expression, role and cooperation in mediating the oxidative burst and degranulation of neutrophils of Brazilian systemic lupus erythematosus patients. Lupus 11:240–248

    Article  PubMed  CAS  Google Scholar 

  15. Enenkel B, Jung D, Frey J (1991) Molecular basis of IgG Fc receptor III defect in a patient with systemic lupus erythematosus. Eur J Immunol 21:659–663

    Article  PubMed  CAS  Google Scholar 

  16. Wilson JG, Ratnoff WD, Schur PH et al (1986) Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus. Arthritis Rheum 29:739–747

    Article  PubMed  CAS  Google Scholar 

  17. Boros P, Odin JA, Chen J et al (1994) Specificity and class distribution of Fc gamma R-specific autoantibodies in patients with autoimmune disease. J Immunol 152:302–306

    PubMed  CAS  Google Scholar 

  18. Witte T, Gessner JE, Gotze O et al (1992) Complement receptor 3 deficiency in systematic lupus erythematosus. Immun Infekt 20:60–61

    PubMed  CAS  Google Scholar 

  19. Lahita RG (1999) The clinical presentation of systemic lupus erythematosus. In: Lahita RG (ed) Systemic lupus erythematosus. Academic, San Diego, CA, pp 325–336

    Google Scholar 

  20. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  PubMed  CAS  Google Scholar 

  21. Bombardier C, Gladman DD, Urowitz MB et al (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  22. Dresser DW (1986) Immunization of experimental animal. In: Weir DM (ed) Handbook of experimental immunology. Blackwell, Oxford, GB, pp 8.1–8.21

    Google Scholar 

  23. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 15:680–685

    Article  Google Scholar 

  24. Gadd KJ, Reid KB (1981) The binding of complement component C3 to antibody antigen aggregates after activation of the alternative pathway in human serum. Biochem J 195:471–480

    PubMed  CAS  Google Scholar 

  25. Lucisano YM, Mantovani B (1984) Lysosomal enzyme release from polymorphonuclear leukocytes induced by immune complexes of IgM and of IgG. J Immunol 132:2015–2020

    PubMed  CAS  Google Scholar 

  26. Cheung K, Archibald AC, Robinson MF (1983) The origin of chemiluminescence produced by neutrophils stimulated by opsonized zymosan. J Immunol 130:2324–2329

    PubMed  CAS  Google Scholar 

  27. Alves CMOS, Marzocchi-Machado CM, Carvalho IF et al (2003) Application of the chemiluminescence systems to evaluate the role of Fcγ and complement receptors in stimulating the oxidative burst in neutrophils. Talanta 60:601–608

    Article  CAS  PubMed  Google Scholar 

  28. Sherer Y, Gorstein A, Fritzler M et al (2004) Autoantibody explosion in Systemic Lupus Erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum 34:501–537

    Article  PubMed  CAS  Google Scholar 

  29. Mir A, Balsalobre B (1994) Inhibition of complement-dependent phagocytosis by autoantibodies against C3b-receptor (CR1) in a case of systemic lupus erythematosus. J Intern Med 235:284–285

    Article  PubMed  CAS  Google Scholar 

  30. Schifferli JA, Peters DK (1983) Complement, the immune-complex lattice, and the pathophysiology of complement-deficiency syndromes. Lancet 2:957–959

    Article  PubMed  CAS  Google Scholar 

  31. Nydegger UE, Kazatchkine MD (1986) Modulation by complement of immune complex processing in health and disease in man. Prog Allergy 39:361–392

    PubMed  CAS  Google Scholar 

  32. Mills JA (1994) Systemic lupus erythematosus. N Engl J Med 330:1871–1879

    Article  PubMed  CAS  Google Scholar 

  33. Ravetch JV, Clynes RA (1998) Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16:421–432

    Article  PubMed  CAS  Google Scholar 

  34. Sylvestre DL, Ravetch JV (1994) Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade. Science 265:1095–1098

    Article  PubMed  CAS  Google Scholar 

  35. Sylvestre D, Clynes R, Ma M et al (1996) Immunoglobulin G-mediated inflammatory responses develop normally in complement deficient mice. J Exp Med 184:2385–2392

    Article  PubMed  CAS  Google Scholar 

  36. Clynes R, Dumitru C, Ravetch JV (1998) Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science 279:1052–1054

    Article  PubMed  CAS  Google Scholar 

  37. Yu CL, Chang KL, Chiu CC et al (1989) Defective phagocytosis, decreased tumour necrosis factor-alpha production, and lymphocyte hyporesponsiveness predispose patients with systemic lupus erythematosus to infections. Scand J Rheumatol 18:97–105

    Article  PubMed  CAS  Google Scholar 

  38. Lucisano YM, De-Mello AM, Vasques ER et al (1998) Precipitated immune complexes of IgM induce the generation of reactive oxygen species by rabbit polymorphonuclear leucocytes. Braz J Med Biol Res 31:793–797

    Article  PubMed  CAS  Google Scholar 

  39. Munoz LE, Herrmann M, Gaipl US (2005) An impaired detection and clearance of dying cells can lead to the development of chronic autoimmunity. Z Rheumatol 64:370–376

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the patients of HCFMRP-USP and the volunteers of the laboratory staff for their cooperation. We also thank Dr Flávio Calil Petean (HC-FMRP-USP) for his help in selecting the SLE patients according to ACR classification criteria and SLEDAI, and Teresa Cristina Lopes Guimarães for secretarial assistance. This study was supported by FAPESP fellowships 98/05462-0 and 96/09626-2.

Author information

Authors and Affiliations

  1. Departamento de Bioquímica e Imunologia da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil

    Celene M. O. S. Alves

  2. Departamento de Imunoparasitologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Minas Gerais, Brasil

    Celene M. O. S. Alves

  3. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil

    Cleni M. Marzocchi-Machado

  4. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Via do Café s/n, Monte Alegre, 14040-903, Ribeirão Preto, São Paulo, Brazil

    Cleni M. Marzocchi-Machado, Ana Elisa C. S. Azzolini, Ana Cristina M. Polizello & Yara M. Lucisano-Valim

  5. Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil

    Paulo Louzada-Junior & Ivan F. de Carvalho

Authors
  1. Celene M. O. S. Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cleni M. Marzocchi-Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paulo Louzada-Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana Elisa C. S. Azzolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Cristina M. Polizello
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ivan F. de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yara M. Lucisano-Valim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Cleni M. Marzocchi-Machado or Yara M. Lucisano-Valim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alves, C.M.O.S., Marzocchi-Machado, C.M., Louzada-Junior, P. et al. Superoxide anion production by neutrophils is associated with prevalent clinical manifestations in systemic lupus erythematosus. Clin Rheumatol 27, 701–708 (2008). https://doi.org/10.1007/s10067-007-0768-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-007-0768-x

Keywords

Search

Navigation