Complement C5a functions as a master switch for the pH balance in neutrophils exerting fundamental immunometabolic effects

Journal of Immunology

Volumn 198, Issue 12, 2017, Pages 4846-4854

  Denk, Stephanie ^a   Neher, Miriam D ^a   Messerer, David A C ^a   Wiegner, Rebecca ^a   Nilsson, Bo ^b   Rittirsch, Daniel ^c   Nilsson Ekdahl, Kristina ^d   Weckbach, Sebastian ^e   Ignatius, Anita ^e   Kalbitz, Miriam ^a   Gebhard, Florian ^a   Weiss, Manfred E ^a   Vogt, Josef ^e   Radermacher, Peter ^e   Köhl, Jörg ^f,g   Lambris, John D ^h   Huber Lang, Markus S ^a  

^a UNIVERSITY HOSPITAL ULM   (Germany)

^b UPPSALA UNIVERSITY   (Sweden)

^c UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^d LINNAEUS UNIVERSITY   (Sweden)

^e UNIVERSITY OF ULM   (Germany)

^f UNIVERSITY OF LÜBECK   (Germany)

^g CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^h UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM; CALMODULIN; COMPLEMENT COMPONENT C5A; GLUCOSE; LACTIC ACID; LACTOFERRIN; MYELOPEROXIDASE; PROTEIN KINASE C; SODIUM PROTON EXCHANGE PROTEIN; ANTACID AGENT; C5AR1 PROTEIN, MOUSE; COMPLEMENT COMPONENT C5A RECEPTOR; LACTIC ACID DERIVATIVE; PEROXIDASE;

ALKALINIZATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CALCIUM CELL LEVEL; CELL PH; CLINICAL ARTICLE; CONTROLLED STUDY; GLUCOSE TRANSPORT; HUMAN; HUMAN CELL; IN VITRO STUDY; INFLAMMATION; INTRACELLULAR SIGNALING; MALE; METABOLISM; MOUSE; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SEPSIS; SEPTIC SHOCK; ANIMAL; CHEMISTRY; COMPLEMENT ACTIVATION; DRUG EFFECTS; IMMUNOLOGY; LEUKOCYTE ACTIVATION; PH; SIGNAL TRANSDUCTION;

ANIMALS; ANTACIDS; CALCIUM; CALMODULIN; COMPLEMENT ACTIVATION; COMPLEMENT C5A; GLUCOSE; HUMANS; HYDROGEN-ION CONCENTRATION; LACTATES; LACTOFERRIN; MICE; NEUTROPHIL ACTIVATION; NEUTROPHILS; PEROXIDASE; PROTEIN KINASE C; RECEPTOR, ANAPHYLATOXIN C5A; SEPSIS; SIGNAL TRANSDUCTION;

EID: 85020485113     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1700393     Document Type: Article

References (53)

1. Matzinger, P. 2002. The danger model: a renewed sense of self. Science 296: 301-305.
2. Hotchkiss, R. S., and I. E. Karl. 2003. The pathophysiology and treatment of sepsis. N. Engl. J. Med. 348: 138-150.
3. Gerard, C. 2003. Complement C5a in the sepsis syndrome-too much of a good thing? N. Engl. J. Med. 348: 167-169.
4. Ward, P. A., and H. Gao. 2009. Sepsis, complement and the dysregulated inflammatory response. J. Cell. Mol. Med. 13: 4154-4160.
5. Ward, P. A. 2004. The dark side of C5a in sepsis. Nat. Rev. Immunol. 4: 133-142.
6. Gerard, N. P., and C. Gerard. 1991. The chemotactic receptor for human C5a anaphylatoxin. Nature 349: 614-617.
7. Fukushima, T., T. K. Waddell, S. Grinstein, G. G. Goss, J. Orlowski, and G. P. Downey. 1996. Na+/H+ exchange activity during phagocytosis in human neutrophils: role of Fcgamma receptors and tyrosine kinases. J. Cell Biol. 132: 1037-1052.
8. Simchowitz, L. 1985. Intracellular pH modulates the generation of superoxide radicals by human neutrophils. J. Clin. Invest. 76: 1079-1089.
9. Grinstein, S., C. J. Swallow, and O. D. Rotstein. 1991. Regulation of cytoplasmic pH in phagocytic cell function and dysfunction. Clin. Biochem. 24: 241-247.
10. Demaurex, N., G. P. Downey, T. K. Waddell, and S. Grinstein. 1996. Intracellular pH regulation during spreading of human neutrophils. J. Cell Biol. 133: 1391-1402.
11. Cardone, R. A., V. Casavola, and S. J. Reshkin. 2005. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat. Rev. Cancer 5: 786-795.
12. Coakley, R. J., C. Taggart, N. G. McElvaney, and S. J. O'Neill. 2002. Cytosolic pH and the inflammatory microenvironment modulate cell death in human neutrophils after phagocytosis. Blood 100: 3383-3391.
13. Lardner, A. 2001. The effects of extracellular pH on immune function. J. Leukoc. Biol. 69: 522-530.
14. Thorsen, K., K. G. Ringdal, K. Strand, E. Søreide, J. Hagemo, and K. Søreide. 2011. Clinical and cellular effects of hypothermia, acidosis and coagulopathy in major injury. Br. J. Surg. 98: 894-907.
15. De Vito, P. 2006. The sodium/hydrogen exchanger: a possible mediator of immunity. Cell. Immunol. 240: 69-85.
16. Hayashi, H., O. Aharonovitz, R. T. Alexander, N. Touret, W. Furuya, J. Orlowski, and S. Grinstein. 2008. Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis. Am. J. Physiol. Cell Physiol. 294: C526-C534.
17. Hinton, A., S. Bond, and M. Forgac. 2009. V-ATPase functions in normal and disease processes. Pflugers Arch. 457: 589-598.
18. Putney, L. K., S. P. Denker, and D. L. Barber. 2002. The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions. Annu. Rev. Pharmacol. Toxicol. 42: 527-552.
19. Ramsey, I. S., E. Ruchti, J. S. Kaczmarek, and D. E. Clapham. 2009. Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst. Proc. Natl. Acad. Sci. USA 106: 7642-7647.
20. Borregaard, N., J. H. Schwartz, and A. I. Tauber. 1984. Proton secretion by stimulated neutrophils. Significance of hexose monophosphate shunt activity as source of electrons and protons for the respiratory burst. J. Clin. Invest. 74: 455-459.
21. Kramer, P. A., S. Ravi, B. Chacko, M. S. Johnson, and V. M. Darley-Usmar. 2014. A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers. Redox Biol. 2: 206-210.
22. Weisdorf, D. J., P. R. Craddock, and H. S. Jacob. 1982. Glycogenolysis versus glucose transport in human granulocytes: differential activation in phagocytosis and chemotaxis. Blood 60: 888-893.
23. Fossati, G., D. A. Moulding, D. G. Spiller, R. J. Moots, M. R. White, and S. W. Edwards. 2003. The mitochondrial network of human neutrophils: role in chemotaxis, phagocytosis, respiratory burst activation, and commitment to apoptosis. J. Immunol. 170: 1964-1972.
24. van Raam, B. J., W. Sluiter, E. de Wit, D. Roos, A. J. Verhoeven, and T. W. Kuijpers. 2008. Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation. PLoS One 3: e2013.
25. Finch, A. M., A. K. Wong, N. J. Paczkowski, S. K. Wadi, D. J. Craik, D. P. Fairlie, and S. M. Taylor. 1999. Low-molecular-weight peptidic and cyclic antagonists of the receptor for the complement factor C5a. J. Med. Chem. 42: 1965-1974.
26. Huber-Lang, M. S., N. C. Riedeman, J. V. Sarma, E. M. Younkin, S. R. McGuire, I. J. Laudes, K. T. Lu, R. F. Guo, T. A. Neff, V. A. Padgaonkar, et al. 2002. Protection of innate immunity by C5aR antagonist in septic mice. FASEB J. 16: 1567-1574.
27. Chow, S., D. Hedley, and I. Tannock. 1996. Flow cytometric calibration of intracellular pH measurements in viable cells using mixtures of weak acids and bases. Cytometry 24: 360-367.
28. Vogt, J. A., D. M. Yarmush, Y. M. Yu, C. Zupke, A. J. Fischman, R. G. Tompkins, and J. F. Burke. 1997. TCA cycle flux estimates from NMRand GC-MS-determined [13C]glutamate isotopomers in liver. Am. J. Physiol. 272: C2049-C2062.
29. Lee, W. N., L. G. Boros, J. Puigjaner, S. Bassilian, S. Lim, and M. Cascante. 1998. Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1, 2-13C2]glucose. Am. J. Physiol. 274: E843-E851.
30. Rittirsch, D., M. S. Huber-Lang, M. A. Flierl, and P. A. Ward. 2009. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat. Protoc. 4: 31-36.
31. Nakae, H., S. Endo, K. Inada, T. Takakuwa, T. Kasai, and M. Yoshida. 1994. Serum complement levels and severity of sepsis. Res. Commun. Chem. Pathol. Pharmacol. 84: 189-195.
32. Unnewehr, H., D. Rittirsch, J. V. Sarma, F. Zetoune, M. A. Flierl, M. Perl, S. Denk, M. Weiss, M. E. Schneider, P. N. Monk, et al. 2013. Changes and regulation of the C5a receptor on neutrophils during septic shock in humans. J. Immunol. 190: 4215-4225.
33. Solomkin, J. S., M. K. Jenkins, R. D. Nelson, D. Chenoweth, and R. L. Simmons. 1981. Neutrophil dysfunction in sepsis. II. Evidence for the role of complement activation products in cellular deactivation. Surgery 90: 319-327.
34. Harfi, I., F. Corazza, S. D'Hondt, and E. Sariban. 2005. Differential calcium regulation of proinflammatory activities in human neutrophils exposed to the neuropeptide pituitary adenylate cyclase-activating protein. J. Immunol. 175: 4091-4102.
35. Merritt, J. E., W. P. Armstrong, C. D. Benham, T. J. Hallam, R. Jacob, A. Jaxa- Chamiec, B. K. Leigh, S. A. McCarthy, K. E. Moores, and T. J. Rink. 1990. SK&F 96365, a novel inhibitor of receptor-mediated calcium entry. Biochem. J. 271: 515-522.
36. Bertrand, B., S. Wakabayashi, T. Ikeda, J. Pouysségur, and M. Shigekawa. 1994. The Na+/H+ exchanger isoform 1 (NHE1) is a novel member of the calmodulinbinding proteins. Identification and characterization of calmodulin-binding sites. J. Biol. Chem. 269: 13703-13709.
37. Wakabayashi, S., B. Bertrand, T. Ikeda, J. Pouysségur, and M. Shigekawa. 1994. Mutation of calmodulin-binding site renders the Na+/H+ exchanger (NHE1) highly H(+)-sensitive and Ca2+ regulation-defective. J. Biol. Chem. 269: 13710-13715.
38. Czermak, B. J., V. Sarma, C. L. Pierson, R. L. Warner, M. Huber-Lang, N. M. Bless, H. Schmal, H. P. Friedl, and P. A. Ward. 1999. Protective effects of C5a blockade in sepsis. Nat. Med. 5: 788-792.
39. Amulic, B., C. Cazalet, G. L. Hayes, K. D. Metzler, and A. Zychlinsky. 2012. Neutrophil function: from mechanisms to disease. Annu. Rev. Immunol. 30: 459-489.
40. Brinkmann, V., U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann, D. S. Weiss, Y. Weinrauch, and A. Zychlinsky. 2004. Neutrophil extracellular traps kill bacteria. Science 303: 1532-1535.
41. Wu, D., H. Dai, J. Arias, L. Latta, and W. M. Abraham. 2009. Low-volume resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor. Crit. Care Med. 37: 1994-1999.
42. Wu, D., and J. Qi. 2012. Mechanisms of the beneficial effect of NHE1 inhibitor in traumatic hemorrhage: inhibition of inflammatory pathways. Resuscitation 83: 774-781.
43. Trivedi, B., and W. H. Danforth. 1966. Effect of pH on the kinetics of frog muscle phosphofructokinase. J. Biol. Chem. 241: 4110-4112.
44. McCall, C. E., D. A. Bass, S. Cousart, and L. R. DeChatelet. 1979. Enhancement of hexose uptake in human polymorphonuclear leukocytes by activated complement component C5a. Proc. Natl. Acad. Sci. USA 76: 5896-5900.
45. Cheng, S. C., J. Quintin, R. A. Cramer, K. M. Shepardson, S. Saeed, V. Kumar, E. J. Giamarellos-Bourboulis, J. H. Martens, N. A. Rao, A. Aghajanirefah, et al. 2014. mTOR- and HIF-1a-mediated aerobic glycolysis as metabolic basis for trained immunity. [Published erratum appears in 2014 Science 346: aaa1503.] Science 345: 1250684.
46. Ayala, A., C. S. Chung, J. L. Lomas, G. Y. Song, L. A. Doughty, S. H. Gregory, W. G. Cioffi, B. W. LeBlanc, J. Reichner, H. H. Simms, and P. S. Grutkoski. 2002. Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Am. J. Pathol. 161: 2283-2294.
47. Cheng, S. C., B. P. Scicluna, R. J. Arts, M. S. Gresnigt, E. Lachmandas, E. J. Giamarellos-Bourboulis, M. Kox, G. R. Manjeri, J. A. Wagenaars, O. L. Cremer, et al. 2016. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nat. Immunol. 17: 406-413.
48. Thomas-Rueddel, D. O., B. Poidinger, M. Weiss, F. Bach, K. Dey, H. Häberle, U. Kaisers, H. Rüddel, D. Schädler, C. Scheer, et al; Medical Education for Sepsis Source Control and Antibiotics Study Group. 2015. Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock. J. Crit. Care 30: 439.e1-439.e6.
49. Huber-Lang, M., V. J. Sarma, K. T. Lu, S. R. McGuire, V. A. Padgaonkar, R. F. Guo, E. M. Younkin, R. G. Kunkel, J. Ding, R. Erickson, et al. 2001. Role of C5a in multiorgan failure during sepsis. J. Immunol. 166: 1193-1199.
50. Ricklin, D., and J. D. Lambris. 2007. Complement-targeted therapeutics. Nat. Biotechnol. 25: 1265-1275.
51. Ricklin, D., G. Hajishengallis, K. Yang, and J. D. Lambris. 2010. Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11: 785-797.
52. Huber-Lang, M., J. V. Sarma, F. S. Zetoune, D. Rittirsch, T. A. Neff, S. R. McGuire, J. D. Lambris, R. L. Warner, M. A. Flierl, L. M. Hoesel, et al. 2006. Generation of C5a in the absence of C3: a new complement activation pathway. Nat. Med. 12: 682-687.
53. Laudes, I. J., J. C. Chu, S. Sikranth, M. Huber-Lang, R. F. Guo, N. Riedemann, J. V. Sarma, A. H. Schmaier, and P. A. Ward. 2002. Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. Am. J. Pathol. 160: 1867-1875.