Abstract
Background
The improved outcome after endoscopic surgery has been attributed to less surgical trauma. However, the underlying mechanisms are not fully understood, and direct effects of CO2 used for pneumoperitoneum, cellular acidification, and/or the lack of air contamination have been postulated to additionally modulate immune functions during endoscopic surgery. We investigated the effects of CO2 incubation, extracellular acidification, and air contamination on the inflammatory response of two distinct macrophage populations.
Methods
R2 and NR 8383 rat macrophage cell lines were used. Interleukin-6 (IL-6) and nitric oxide after lipopolysaccharide (LPS) stimulation were determined in these sets of experiments: incubation in 100% CO2, 5% CO2, and room air for 2h; incubation at pH 7.4, 6.5, and 5.5 for 2 h in 5% CO2; and incubation in 100% CO2, 5% CO2 and room air in fixed pH 6.3. The extracellular pH was monitored during incubation. We determined the alteration of intracellular pH in cells subjected to extracellular acidification by fluorescence microscopy.
Results
Extracellular pH decreased to 6.3 during 100% CO2 incubation. IL-6 release was reduced after CO2 incubation in NR 8383 cells and increased in R2 cells (p < 0.05). It was not altered by air incubation. Decreasing the extracellular pH to 6.5 mimicked the effects of CO2 and a decrease to 5.5 suppressed IL-6 release in both cell lines. In fixed pH at 6.3, CO2 and air incubation had no effect. CO2 and pH had no impact on nitric oxide release and vitality. Intracellular pH decreased with extracellular acidification without significant difference between the two cell lines.
Conclusions
A decrease in extracellular pH during incubation in CO2 differentially affects IL-6 release in macrophage subpopulations. This may explain contradictory results in the literature. Moreover, we demonstrated that air contamination does not affect macrophage cytokine release. The decrease in extracellular pH is the primary underlying mechanism of the alteration of macrophage cytokine release after CO2 incubation, and it appears that the ability to maintain intracellular pH is not determined by the effects of CO2 or extracellular acidification.
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References
Bellocq A, Suberville S, Philippe C, Bertrand F, Perez J, Fouqueray B, Cherqui G, Baud L (1998) Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages. Evidence for involvement of nuclear factor-kappaB activation. J Biol Chem 273:5086–5092
Bidani A, Wang CZ, Saggi SJ, Heming TA (1998) Evidence for pH sensitivity of tumor necrosis factor-alpha release by alveolar macrophages. Lung 176:111–121
Busche R, Jeromin A, von Engelhardt W, Rechkemmer G (1993) Basolateral mechanisms of intracellular pH regulation in the colonic epithelial cell line HT29 clone 19A. Pflügers Arch 425:219–224
Gallery MP (2003) Expansion beyond compression. Surg Endosc 17:A23–A25
Gjomarkaj M, Pace E, Melis M, Spatafora M, Profita M, Vignola AM, Bonsignore G, Toews GB (1998) Phenotypic and functional characterization of normal rat pleural macrophages in comparison with autologous peritoneal and alveolar macrophages. Am J Respir Cell Mol Biol 20:135–142
Gupta A, Watson DI (2001) Effect of laparoscopy on immune function. Br J Surg 88:1296–1306
Heming TA, Dave SK, Tuazon DM, Chopra AK, Peterson JW, Bidani A (2001) Effects of extracellular pH on tumour necrosis factor-α production by resident alveolar macrophages. Clin Sci 101:267–274
Heming TA, Tuazon DM, Dave SK, Chopra AK, Peterson JW, Bidani A (2001) Post-transcriptional effects of extracellular pH on tumour necrosis factor-α production in RAW 246.7 and J774 A.I cells Clin Sci 101:259–266
Huang CJ, Haque IU, Slovin PN, Nielsen RB, Fang X, Skimming JW (2002) Environmental pH regulates LPS-induced nitric oxide formation in murine macrophages. Nitric Oxide 6:73–78
Kopernik G, Avinoach E, Grossman Y, Levy R, Yulzari R, Rogachev B, Douvdevani A (1998) The effect of a high partial pressure of carbon dioxide environment on metabolism and immune functions of human peritoneal cells–relevance to carbon dioxide pneumoperitoneum. Am J Obstet Gynecol 179:1503–1510
Lardner A (1999) The effects of extracellular pH on immune function. J Leukoc Biol 69:522–530
Neuhaus SJ, Watson DI, Ellis T, Lafullard , Jamieson GG, Russel J (2001) Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study. ANZ J Surg 71:447–452
Neuhaus SJ, Watson DI, Ellis T, Rofe AM, Mathew G, Jamieson GG (2000) Influence of gases on intraperitoneal immunity during laparoscopy in tumor-bearing rats World J Surg 24:1227–1231
Ozmen MM, Kessaf Aslar A, Besler HT, Cinel I (2002) Does splanchnic ischemia occur during laparoscopic cholecystectomy? Surg Endosc 16:468–471
Romeo C, Impellizzeri P, Antonuccio P, Turiaco N, Cifala S, Gentile C, Passaniti M, Marini H, Squadrito F, Altavilla D (2003) Peritoneal macrophage activity after laparoscopy or laparotomy. J Pediatr Surg 38:97–101
Tung PH, Smit0h CD (1999) Laparoscopic insufflation with room air causes exaggerated interleukin-6 response. Surg Endosc 13:473–475
Ure BM, Niewold TA, Bax A, Ham M, van der Zee DC, Essen GJ (2002) Peritoneal, systemic, and distant organ inflammatory responses are reduced by a laparoscopic approach and carbon dioxode vs air. Surg Endosc 16:836–842
van den Berg TK, Dopp EA, Dijkstra CD (2001) Rat macrophages: membrane glycoproteins in differentiation and function. Immunol Rev 184:45–57
Watson RW, Redmond HP, McCarthy J, Burke PE, Bouchier-Hayes D (1995) Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine model. Br J Surg 82:1060–1065
West MA, Baker J, Bellingham J (1996) Kinetics of decreased LPS-stimulated cytokine release by macrophages exposed to CO2. J Surg Res 63:269–274
West MA, Hackman DJ, Baker J, Rodriguez JL, Bellingham J, Rotstein OD (1997) Mechanism of decreased in vitro murine macrophage cytokine release after exposure to carbon dioxide. Ann Surg 226:179–190
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Kos, M., Kuebler, J.F., Jesch, N.K. et al. Carbon dioxide differentially affects the cytokine release of macrophage subpopulations exclusively via alteration of extracellular pH. Surg Endosc 20, 570–576 (2006). https://doi.org/10.1007/s00464-004-2175-6
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DOI: https://doi.org/10.1007/s00464-004-2175-6