Mini-laparotomy and full laparotomy, but not laparoscopy, alter hepatic macrophage populations in a rat model

  • N. K. Jesch
  • G. Vieten
  • T. Tschernig
  • W. Schroedel
  • B. M. Ure
Original article



Immune function is better preserved by laparoscopic versus conventional surgery. Numerous mediators of the systemic trauma response are synthesized and/or regulated by the liver. However, it has been stated that the advantages of laparoscopic surgery are no more obvious when conventional operations are performed via mini-laparotomy. We set out to compare the impact of laparoscopy and mini- and full laparotomy on the hepatic macrophage populations.


Male Lewis rats were subjected to anesthesia alone (control), mini-laparotomy (1 cm), full laparotomy (7 cm), or laparoscopy for 60 min. Endpoints were the total protein in the peritoneal lavage fluid, hepatic ED-1 cells (recruited monocytes), hepatic ED-2 cells (Kupffer cells), the expression of OX-6 in the liver, and C-reactive protein (CRP) in plasma.


Protein in the peritoneal lavage fluid increased significantly after all interventions. Full laparotomy was accompanied by an enhancement in ED-1-positive monocytes in the liver parenchyma compared to all other groups (p < 0.001). Mini- and full laparotomy led to an increase in ED-2-positive Kupffer cells (p < 0.001). Laparoscopy did not affect the number of monocytes/macrophages. There was no significant alteration of OX-6 expression in either group. No change in the cellular composition in the periportal fields was observed. The CRP plasma levels did not significantly differ between groups.


Laparoscopy completely prevents hepatic macrophage populations from expansion and normal cell disposition is preserved. Laparotomy, irrespective of incision size, increases the number of Kupffer cells. Moreover, full laparotomy, but not mini-laparotomy or laparoscopy, causes an increase in hepatic monocyte recruitment. The regulating pathways after surgery differ from other immunologic challenges, such as sepsis, in which immunocompetent cells accumulate and are stimulated in the periportal fields.


Laparoscopy Laparotomy Rat Liver Macrophage Monocyte 



The excellent technical assistance of Karin Westemann is very much appreciated. This research was supported by a grant (HiLF) from the Hannover Medical School, Hannover, Germany.


  1. 1.
    Allendorf, JD, Bessler, M, Whelan, RL, Trokel, M, Laird, DA, Terry, MB, Treat, MR 1997Postoperative immune function varies inversely with the degree of surgical trauma in a murine modelSurg Endosc11427430CrossRefPubMedGoogle Scholar
  2. 2.
    Ayala, A, O’Neill, PJ, Uebele, SA, Herdon, CD, Chaudry, ICH 1997Mechanism of splenic immunosuppression during sepsis: key role of Kupffer cell mediatorsJ Trauma42882888PubMedGoogle Scholar
  3. 3.
    Bouwens, L, Baekeland, M, Zanger, R, Wisse, E 1986Quantitation, tissue distribution and proliferation kinetics of Kupffer cells in normal rat liverHepatology6718722PubMedGoogle Scholar
  4. 4.
    Collier, DS, Pain, JA, Wight, DG, Lovat, P, Bailey, ME 1986The Kupffer cell in experimental extrahepatic cholestasis in the rat — a light microscopy, immunohistochemical and electron microscopy studyJ Pathol150187194CrossRefPubMedGoogle Scholar
  5. 5.
    Decker, T, Lohmann-Matthes, ML, Karck, U, Peters, T, Decker, K 1989Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophagesJ Leukoc Biol45139146PubMedGoogle Scholar
  6. 6.
    Dhainaut, JF, Marin, N, Mignon, A, Vinsonneau, C 2001Hepatic response to sepsis: interaction between coagulation and inflammatory processesCrit Care Med29S42S47CrossRefPubMedGoogle Scholar
  7. 7.
    Garcia-Caballero, M, Vara-Thorbeck, C 1993The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatmentSurg Endosc7416419CrossRefPubMedGoogle Scholar
  8. 8.
    Glaser, F, Sannwald, GA, Buhr, HJ, Kuntz, C, Mayer, H, Klee, F, Herfarth, C 1995General stress response to conventional and laparoscopic cholecystectomyAnn Surg221372380PubMedGoogle Scholar
  9. 9.
    Grande M, Tucci GF, Adorisio O, Barini A, Rulli F, Neri A, Franchi F, Farinon AM (2002) Systemic acute-phase response after laparoscopic and open cholecystectomy. Surg Endosc, DOI: 10.1007/s0046400190425, November 12Google Scholar
  10. 10.
    Gutt, CN, Riemer, V, Brier, C, Berguer, R, Paolucci, V 1998Standardized technique of laparoscopic surgery in the ratDig Surg15135139CrossRefPubMedGoogle Scholar
  11. 11.
    Imada, K, Fukuda, Y, Koyama, Y, Nakano, I, Yamada, M, Katano, Y, Hayakawa, T 1997Naive and memory T cell infiltrates in chronic hepatitis C: phenotypic changes with interferon treatmentClin Exp Immunol1095966CrossRefPubMedGoogle Scholar
  12. 12.
    Kloosterman, T, Blomberg, BM, Borgstein, P, Cuesta, MA, Scheper, RJ, Meijer, S 1994Unimpaired immune functions after laparoscopic cholecystectomySurgery115424428PubMedGoogle Scholar
  13. 13.
    Kmiec, Z 2001Cooperation of liver cells in health and diseaseAdv Anat Embryol Cell Biol1611151Google Scholar
  14. 14.
    Knolle, PA, Gerken, G 2000Local control of the immune response in the liverImmunol Rev1742134CrossRefPubMedGoogle Scholar
  15. 15.
    Lauterschlager, I 1984Characteristic of the strongly Ia-positive cells in rat liverScand J Immunol20333338PubMedGoogle Scholar
  16. 16.
    Lowry, OH, Rosebough, NJ, Farr, AL, Randall, RJ 1951Protein measurement with the Folin phenol reagentJ Biol Chem193265275PubMedGoogle Scholar
  17. 17.
    Luettig, B, Pape, L, Bode, U, Bell, EB, Sparshott, SM, Wagner, S, Westermann, J 1999Naive and memory T lymphocytes migrate in comparable numbers through normal rat liver: activated T cells accumulate in the periportal fieldJ Immunol16343004307PubMedGoogle Scholar
  18. 18.
    McMahon, AJ, O’Dwyer, PJ, Cruikshank, AM, McMillan, DC, O’Reilly, DS, Lowe, GD, Rumley, A, Logan, RW, Baxter, JN 1993Comparison of metabolic responses to laparoscopic and minilaparotomy cholecystectomyBr J Surg8012551258PubMedGoogle Scholar
  19. 19.
    Nave, H, Hoersten, S, Helfritz, F, Kuhlmann, S, Ballof, J, Drube, J, Pabst, R 1998Intravenous cannulation of the freely behaving rat: frequent blood sampling and volume-dependent effect on blood leukocyte countsJ Exp Anim Sci396777Google Scholar
  20. 20.
    Nguyen, NT, Braley, S, Fleming, NW, Lambourne, L, Rivers, R, Wolfe, BM 2003Comparison of postoperative hepatic function after laparoscopic versus open gastric bypassAm J Surg1864044CrossRefPubMedGoogle Scholar
  21. 21.
    Pannen, BH, Robotham, JL 1995The acute-phase responseNew Horizons3183197PubMedGoogle Scholar
  22. 22.
    Redmond, HP, Watson, RW, Houghton, T, Condron, C, Watson, RG, Bouchier-Hayes, D 1994Immune function in patients undergoing open vs laparoscopic cholecystectomyArch Surg12912401246PubMedGoogle Scholar
  23. 23.
    Rogers, AB, Fox, JG 2004Inflammation and cancer. I. Rodent models of infectious gastrointestinal and liver cancerAm J Physiol Gastrointest Liver Physiol286G361G366CrossRefPubMedGoogle Scholar
  24. 24.
    Rosenthal, AS 1978Determinant selection and macrophage function in genetic control of the immune responseImmunol Rev40136152PubMedGoogle Scholar
  25. 25.
    Sietses, C, Blomberg, ME, Eijsbouts, QA, Beelen, RH, Berends, FJ, Cuesta, MA 2002The influence of CO2 versus helium insufflation or the abdominal wall lifting technique on the systemic immune responseSurg Endosc16525528CrossRefPubMedGoogle Scholar
  26. 26.
    Suffredini, AF, Fantuzzi, G, Badolato, R, Oppenheim, JJ, O’Grady, NP 1999New insights into the biology of the acute phase responseJ Clin Immunol19203214CrossRefPubMedGoogle Scholar
  27. 27.
    Tsutsui, H, Adachi, K, Seki, E, Nakanishi, K 2003Cytokine-induced inflammatory liver injuriesCurr Mol Med3545559CrossRefPubMedGoogle Scholar
  28. 28.
    Ure, BM, Niewold, TA, Bax, NM, Ham, M, Zee, DC, Essen, GJ 2002Peritoneal, systemic, and distant organ inflammatory responses are reduced by a laparoscopic approach and carbon dioxide versus airSurg Endosc16836842CrossRefPubMedGoogle Scholar
  29. 29.
    Vittimberga, FJ, Nolan, B, Perugini, RA, Spector, L, Gallery, MP 2000Laparoscopic surgery and Kupffer cell activationSurg Endosc1411711176CrossRefPubMedGoogle Scholar
  30. 30.
    Watson, RW, Redmond, HP, McCarthy, J, Burke, PE, Bouchier-Hayes, D 1995Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine modelBr J Surg8210601065PubMedGoogle Scholar
  31. 31.
    West, MA, Hackam, DJ, Baker, J, Rodriguez, JL, Bellingham, J, Rotstein, OD 1997Mechanism of decreased in vitro murine macrophage cytokine release after exposure to dioxide: relevance to laparoscopic surgeryAnn Surg226179190CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • N. K. Jesch
    • 1
  • G. Vieten
    • 1
  • T. Tschernig
    • 2
  • W. Schroedel
    • 3
  • B. M. Ure
    • 1
  1. 1.Department of Pediatric SurgeryHannover Medical SchoolHannoverGermany
  2. 2.Department of Functional and Applied AnatomyHannover Medical SchoolHannoverGermany
  3. 3.Institute of Bacteriology and Mycology, Faculty of Veterinary MedicineUniversity of LeipzigLeipzigGermany

Personalised recommendations