Mechanism of Decreased In Vitro Murine Macrophage Cytokine Release After Exposure to Carbon Dioxide

West, Michael A.; Hackam, David J.; Baker, Jeffrey B.; Rodriguez, Jorge Luis; Bellingham, Janet; Rotstein, Ori D.

doi:10.1097/00000658-199708000-00010

Cited by 167 publications

(130 citation statements)

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“…For example, acidic pH regulates neutrophil functions, including the stimulation of superoxide anion production (4), inhibition of chemotaxis (5), and stimulation of endocytosis and Ag presentation (6), and dendritic cell function, including the stimulation of maturation and production of IL-12 (7). As for macrophages, the acidification-induced modulation of the cell functions has been implicated to be involved in less surgical trauma in laparoscopic surgery compared with an operation through a laparotomy (8,9). Thus, abdominal insufflation with CO 2 decreased LPS-induced TNF-␣ production from peritoneal macrophages and the serum TNF-␣ level in association with a pH decrease in the abdominal cavity (8,9) and prevented mortality from LPS-induced sepsis in animal models (10).…”

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confidence: 99%

“…As for macrophages, the acidification-induced modulation of the cell functions has been implicated to be involved in less surgical trauma in laparoscopic surgery compared with an operation through a laparotomy (8,9). Thus, abdominal insufflation with CO 2 decreased LPS-induced TNF-␣ production from peritoneal macrophages and the serum TNF-␣ level in association with a pH decrease in the abdominal cavity (8,9) and prevented mortality from LPS-induced sepsis in animal models (10). Acidification of the peritoneal cavity by buffered acidic lavage solutions other than CO 2 pneumoperitoneum also reduced the serum TNF-␣ levels (9).…”

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confidence: 99%

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Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Proinflammatory Cytokine Production in Peritoneal Macrophages

Mogi¹,

Tobo²,

Tomura³

et al. 2009

The Journal of Immunology

144

125

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Extracellular acidification inhibited LPS-induced TNF-α protein production, which was associated with an inhibition of TNF-α mRNA expression, in mouse peritoneal macrophages. The LPS-induced cytokine production was also inhibited by Gs protein-coupled receptor agonists prostaglandin E1 and isoproterenol. Among OGR1 family proton-sensing GTP-binding regulatory protein-coupled receptors, TDAG8, OGR1, and G2A are expressed in the cells. The inhibitory action by acidic pH on TNF-α production was significantly attenuated in macrophages from TDAG8Tp/Tp mice but not in those from OGR1geo/geo mice. Moreover, small interfering RNA specific to TDAG8, but not to G2A, clearly attenuated the acidification-induced inhibition of TNF-α production. On the other hand, the down-regulation or deficiency of TDAG8 hardly affected prostaglandin E1- or isoproterenol-induced actions. LPS-induced IL-6 production was also inhibited by extracellular acidification in a manner that was sensitive to TDAG8 expression. The acidic pH-induced inhibitory action on the cytokine production was significantly reversed either by a small interfering RNA specific to Gs proteins or by a protein kinase A (PKA)-specific inhibitor H89. Indeed, a PKA-specific cAMP derivative inhibited LPS-induced cytokine production. Moreover, acidification induced cAMP accumulation in a TDAG8-specific way. We conclude that TDAG8, at least partly, mediates the extracellular acidification-induced inhibition of proinflammatory cytokine production through the Gs protein/cAMP/PKA signaling pathway in mouse macrophages.

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confidence: 99%

mentioning

confidence: 99%

Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Proinflammatory Cytokine Production in Peritoneal Macrophages

Mogi¹,

Tobo²,

Tomura³

et al. 2009

The Journal of Immunology

144

125

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“…In the present study the PNP and PNP/CLP rats exhibited arterial, intraperitoneal and subperitoneal acidosis, suggesting intracellular acidosis. West et al 32 have proposed relative intracellular acidosis as the mechanism by which the decrease in cytokines is exerted 29 . Redmond et al 30 showed that circulating monocytes obtained from patients after laparoscopic cholecystectomy exhibited reduced TNF release compared to those from patients who had open cholecystectomy.…”

Section: Discussionmentioning

confidence: 99%

Influence of laparoscopy and laparotomy on gasometry, leukocytes and cytokines in a rat abdominal sepsis model

et al. 2006

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Purpose: Laparoscopic surgery is associated with reduced surgical trauma, and less acute phase response, as compared with open surgery. Cytokines are important regulators of the biological response to surgical and anesthetic stress. The aim of this study was to determine if CO 2 pneumoperitoneum would change cytokine expression, gas parameters and leukocyte count in septic rats. Methods: Wistar rats were randomly assigned to five groups: control (anesthesia only), laparotomy, CO 2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and laparoscopic cecum ligation and puncture. After 30 min of the procedures, arterial blood samples were obtained to determine leukocytes subpopulations by hemocytometer. TNFα, IL-1β, IL-6 were determined in intraperitoneal fluid (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and subperitoneal exsudates. Results: Peritoneal TNFα, IL-1β and IL-6 concentrations were lower in pneumoperitoneum rats than in all other groups (p<0.05). TNFα, IL-1β and IL-6 expression was lower in the laparoscopic than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and puncture group developed significant hypercarbic acidosis in blood and subperitoneal fluid when compared to open procedure group. Total white blood cells and lymphocytes were significantly lower in laparoscopic cecum ligation and puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic cecum ligation rats had a significant increase in blood neutrophils and eosinophils when compared with controls (p<0.05). Conclusions: This study demonstrates that the CO 2 pneumoperitoneum reduced the inflammatory response in an animal model of peritonitis with respect to intraperitoneal cytokines, white blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced hypercarbic acidosis in septic animals. Key words: Pneumoperitoneum. Carbon Dioxide. Sepsis. Acidosis. Leucocytes. RESUMO Objetivo:A cirurgia laparoscópica está associada com trauma reduzido e baixa resposta na fase aguda do trauma, quando comparada com a cirurgia aberta. As citocinas e o balanço ácido-base são fatores importantes da resposta biológica ao trauma cirúrgico-anestésico. O objetivo deste estudo foi determinar se o pneumoperitôneo com CO 2 altera a expressão das citocinas, a gasometria e a contagem diferencial de leucócitos em ratos com sepse abdominal. Métodos: Ratos Wistar foram aleatoriamente distribuídos em 5 grupos: controle (somente anestesia), laparotomia, pneumoperitôneo com CO 2 , ligadura e punção do ceco por laparotomia, ligadura e punção do ceco por laparoscopia. Após 30 minutos dos procedimentos, sangue arterial foi colhido para leucometria diferencial em hemocitômetro. TNFα, IL-1β e IL-6 foram dosadas no líquido intraperitoneal (por ELISA). Os parâmetros gasosos foram medidos no sangue arterial e nos exsudatos intraperitoneal e subperitoneal. Resultados: Os valores de TNFα, IL-1β e IL-6 foram significantemente menores nos ratos submetidos ao pneumoperitôneo do que em...

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“…8 Despite the benefit in decreased systemic cell mediated immune suppression associated with laparoscopy, CO 2 has been shown to result in an acidotic intraperitoneal environment and impaired peritoneal macrophage function contributing to local tumor implantation. [9][10][11] But still use of wound protectors and specimen extraction bags to prevent direct contamination of incision sites and use of a general cytotoxic substance like povidone-iodine were excellent in preventing port-site incisional tumor implantation after laparoscopy. b.…”

Section: Various Operative Techniques Availablementioning

confidence: 99%

Laparoscopy in Colorectal Malignancies: Current Concepts

Bharatam¹

2010

WJOLS

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Mechanism of Decreased In Vitro Murine Macrophage Cytokine Release After Exposure to Carbon Dioxide

Abstract: The authors propose that cellular acidification induced by peritoneal CO2 insufflation contributes to blunting of the local inflammatory response during laparoscopic surgery.

Cited by 167 publications

References 23 publications

Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Proinflammatory Cytokine Production in Peritoneal Macrophages

Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Proinflammatory Cytokine Production in Peritoneal Macrophages

Influence of laparoscopy and laparotomy on gasometry, leukocytes and cytokines in a rat abdominal sepsis model

Laparoscopy in Colorectal Malignancies: Current Concepts

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