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Abberant Cytosolic Calcium Ion Mobilization in Chronic Granulomatous Disease Neutrophils

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Abstract

Beside the inability to produce superoxide ions, neutrophils (PMN) from chronic granulomatous disease (CGD) patients show other functional defects, e.g. abnormal membrane potential reactions. We observed that PMN from a female CGD carrier, with a discrete mutation in one allele of the pg91phox gene and exhibiting extreme lyonization, showed a consistently and remarkably delayed PMN cytosolic calcium response to the tripeptide fMLP or leukotriene B4 (LTB4). In keeping with results from other CGD patients, membrane potential changes were abnormal, whereas chemotaxis and adherence was normal. Since phospholipase D-generated metabolites are important for calcium transients we examined the generation of phosphatidic acid, but found that to be normal. A male CGD patient with pg91phox deficiency exhibited a trend toward prolongation of this calcium response, whereas two other CGD patients (one with p47 and one with 67phox deficiencies) had normal calcium transients. Thus, our finding points to a defect of the stimulus response coupling for fMLP and LTB4, which is supposed to be characteristic for this patient or a subset of CGD patients.

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REFERENCES

  1. Segal, B. H., T. L. Leto, J. I. Gallin, H. L. Malech, and S. M. Holland. 2000. Genetic, biochemical and clinical features of chronic granulomatous disease. Medicine 79:170-200.

    Article  PubMed  Google Scholar 

  2. Åhlin, A., M. de Boer, D. Roos, J. Leusen, C. I. E. Smith, U. Sundin, H. Rabbani, J. Palmblad, and G. Elinder, 1995. Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. Acta Paediatr. 84:1386-1394.

    PubMed  Google Scholar 

  3. Roos, D., M. de Boer, F. Kuribayashi, C. Meischl, R. Weening, A. W. Segal, A. Åhlin, K. Nemet, J. P. Hossle, E. Bernatowska-Matuszkiewicz, and H. Middelton-Price, 1996. Mutations in the X-linked and autosomal recessive forms of chronic granulomatous disease. Blood 87:1663-1681.

    PubMed  Google Scholar 

  4. Rosen-Wolff, A., W. Soldan, K. Heyne, J. Bickhardt, M. Gahr, and J. Roesler. 2001. Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatusinfection associated with age-related skewing of lyonization. Ann. Hematol. 80:113-115.

    Article  PubMed  Google Scholar 

  5. Seligmann, B. E. and JI. Gallin. 1980. Use of lipophilic probes of membrane potential to assess human neutrophil activation: Abnormality in chronic granulomatous disease. J. Clin. Invest. 66:493-503.

    PubMed  Google Scholar 

  6. Segal, A.W. 1985. Variations on the theme of chronic granulomatous disease. Lancet i:1378-1383.

    Article  Google Scholar 

  7. Gold, S. B., D. M. Hanes, D. P. Stites, and H. H. Fudenberg. 1974. Abnormal kinetics of degranulation in chronic granulomatous disease. N. Engl. J. Med. 291:332-337.

    PubMed  Google Scholar 

  8. Nath, J. and J. I. Gallin. 1983. Studies in normal and chronic granulomatous disease neutrophils indicate a correlation of tubulin tyrosinolation with the cellular redox state. J. Clin. Invest. 71:1273-1281.

    PubMed  Google Scholar 

  9. Åhlin, A., H. Gyllenhammar, B. Ringertz, and J. Palmblad. 1995. Leukotriene B4 induced membrane potential changes and aggregation kinetics in neutrophils from patients with chronic granulomatous disease-Relation to pH changes. J. Lab. Clin. Med. 125:392-401.

    PubMed  Google Scholar 

  10. Geiszt, M., A. Kapus, and E. Ligeti 2001. Chronic granulomatous disease: More than the lack of superoxide? J. Leukocyte. Biol. 69:191-6.

    PubMed  Google Scholar 

  11. Maturana, A., S. Arnaudeau, S. Ryser, Banfi B, JP. Hossle, W. Schlegel, K. H. Krause, and N. Demaurex. 2001. Heme histidine ligands within the gp91 phoxmodulate proton conduction by the phagocyte NADPH oxidase. J. Biol. Chem. 276:30277-30284.

    Article  PubMed  Google Scholar 

  12. Leusen, J. H. W., C. Meischl, M. H. M. Eppink, P. M. Hilarius, M. de Boer, R. S. Weening, A. Åhlin, D. Sanders, D. Goldblatt, H. Skopczynska, E. Bernatowska, J. Palmblad, A. J. Verhoeven, W. J. H. van Berkel, and D. Roos. 2000. Four novel mutations in the gene encoding pg91-phox of human NADPH oxidase: consequences for oxidase assembly. Blood 95:666-73

    PubMed  Google Scholar 

  13. Leusen, J. H.W., A. de Klein, P.M. Hilarius, A. Åhlin, J. Palmblad, C. I. E. Smith, D. Diekman, A. Hall, A. J. Verhoeven, and D. Roos. 1996. Disturbed interaction of p21-rac with mutated p67-phox causes chronic granulomatous disease. J. Exp. Med. 184:1243-1249.

    Article  PubMed  Google Scholar 

  14. Ringertz, B., J. Palmblad, J. Å. Lindgren. 1985. Stimulus-specific neutrophil aggregation-evaluation of possible mechanisms for the stimulus-response apparatus. J. Clin. Lab. Med. 106 :132-140.

    Google Scholar 

  15. Palmblad, J., H. Gyllenhammar, B. Ringertz, E. Nilsson, B. Cottell, and B. Leukotriene. 1988. triggers highly characteristic and specific functional responses in neutrophils: Studies of stimulus specific mechanisms. Biochem. Biophys. Acta 970:92-102.

    Article  Google Scholar 

  16. Nilsson, E., T. Andersson, M. Fällman, K. Rosendahl, and J. Palmblad. 1992. Effects of ethanol on the chemotactic peptideinduced secand messenger generation and superoxide production in polymorphonuclear leukocytes. J. Infect. Dis. 166:854-860.

    PubMed  Google Scholar 

  17. Palmblad, J., R. Lerner, and S. Larsson. 1994. Signal transduction mechanisms for leukotriene B4 induced hyperadhesiveness of endothelial cells for neutrophils. J. Immunol. 152:262-269.

    PubMed  Google Scholar 

  18. Heimburger, M, and J. Palmblad. 1996. Effects of leukotriene C4 and D4 on endothelial cell hyperadhesivity for neutrophils. Clin. Exp. Immunol. 103:454-460.

    PubMed  Google Scholar 

  19. Palmblad, J., R. W. Wannemacher, N. Salem, D. B. Kuhns, and D. G. Wright. 1998. Essential fatty acid deficiency and neutrophil function: Studies of lipid-free total parenteral nutrition in monkeys. J. Lab. Clin. Med. 111:634-644.

    Google Scholar 

  20. Samuelsson, J., A. Hansson, K. Rosendahl, and J. Palmblad. 1993. Superoxide anion production and phospholipase D mediated generation of diacylglycerol is reduced after fMLP stimulation of PMN granulocytes in polycytemia vera. J. Lab. Clin. Med. 121:310-319.

    PubMed  Google Scholar 

  21. Billah, M. M., S. Eckel, T. J. Mullman, R. W. Egan, and M. I. Siegel.1989. Phosphatidyl choline hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. J. Biol. Chem. 264:17069-1777.

    PubMed  Google Scholar 

  22. Geiszt, M., A. Kapus, K. Nemet, L. Farkas, and E. Ligeti. 1997. Regulation of capacitative Ca2+ influx in human neutrophil granulocytes. J. Biol. Chem. 272:26471-26478.

    Article  PubMed  Google Scholar 

  23. Ambuso, D. R., G. Thurman, C. C. Silliman, and S. M. Anderson. 1995. Variant chronic granulomatous disease associated with diminished phosphorylation on tyrosine of a 105 kDa protein. BloodSuppl. 1:27A

    Google Scholar 

  24. Tintinger, G. R., A. J. Theron, H. C. Steel, and R. Anderson. 2001 Accelerated calcium influx and hyperactivation of neutrophils in chronic granulomatous disease. Clin. Exp. Immunol. 123:254-263.

    Article  PubMed  Google Scholar 

  25. Rada, B. K., M. Geiszt, R. van Bruggen, K. Nemet, D. Roos, and E. Ligeti. 2003. Calcium signalling is altered in myeloid cells with a deficiency inNADPH oxidase activity. Clin. Exp. Immunol. 132:53-60.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. The Center for Inflammation and Hematology Research, Departments of Hematology, Endocrinology, Rheumatology and Pediatrics, Karolinska University Hospital, Huddinge and Solna, Sweden

    Jan Palmblad, Jan Palmblad, Anders Hansson, Mikael Heimbürger & Anders Åhlin

  2. Sachs' Children's Hospital, Stockholm, Sweden

    Anders Hansson, Mikael Heimbürger & Anders Åhlin

Authors
  1. Jan Palmblad
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  2. Anders Hansson
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  3. Mikael Heimbürger
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  4. Anders Åhlin
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Correspondence to Jan Palmblad.

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Palmblad, J., Hansson, A., Heimbürger, M. et al. Abberant Cytosolic Calcium Ion Mobilization in Chronic Granulomatous Disease Neutrophils. Inflammation 28, 133–138 (2004). https://doi.org/10.1023/B:IFLA.0000039559.96659.d9

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  • DOI: https://doi.org/10.1023/B:IFLA.0000039559.96659.d9

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