Ketamine Decreases Phagocytic Capacity of Canine Peripheral Blood Phagocytes In Vitro

In Vitro에서 개 말초혈액 탐식세포의 탐식능에 대한 케타민의 효과

  • Kang, Ji-Houn (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Min-Jun (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Yang, Mhan-Pyo (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
  • 강지훈 (충북대학교 수의과대학 수의내과학교실 및 동물의학연구소) ;
  • 김민준 (충북대학교 수의과대학 수의내과학교실 및 동물의학연구소) ;
  • 양만표 (충북대학교 수의과대학 수의내과학교실 및 동물의학연구소)
  • Published : 2008.04.30

Abstract

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and a short-acting general anaesthetic agent for human and veterinary use. We previously reported that treatment with ketamine impairs oxidative burst activity of canine peripheral blood leukocytes. In this study, the effect of ketamine on phagocytic capacity of canine peripheral blood leukocytes was examined in vitro. Phagocytic capacity was analyzed by using a flow cytometry. Ketamine directly decreased the phagocytic capacity of peripheral blood polymorphonuclear cells (PMN) and monocytes but not total peripheral blood mononuclear cells (PBMC). In addition, the phagocytic capacity of PMN and monocytes was inhibited by the ketamine-treated PBMC but not PMN culture supernatant. These results suggest that ketamine has a direct inhibitory effect on the phagocytic capacity of canine peripheral blood phagocytes and involves the production of soluble factor(s) from canine PBMC, which may suppress the phagocytic capacity.

케타민은 N-methyl-D-aspartate (NMDA) 수용체의 비경쟁적인 길항제로 인의와 수의학에서 전신 마취제로 사용하는 약물이다. 본 연구진은 이전에 케타민이 개 말초혈액 백혈구의 순간산소과소비현상(oxidative burst activity)을 손상시킨다고 보고하였다. 현재 연구에서는 개 말초혈액 탐식세포의 탐식능(phagocytic capacity)에 대한 케타민의 효과를 검토하였다. 탐식능은 유세포 분석기로 분석하였다. 말초혈액 다형핵백혈구(peripheral blood polymorphonuclear cells; PMN)와 단구(monocytes)의 탐식능은 케타민의 직접 처리에 의해 감소하였으나 단핵구세포(peripheral blood mononuclear cells; PBMC) 분획에서의 탐식능은 케타민의 직접 처리에 의해 변화가 없었다. 말초혈액 다형핵백혈구와 단구의 탐식능은 케타민을 처리한 단핵구세포 배양상층액에 의해서도 감소하였다. 이상의 결과로부터 케타민은 호중구와 단구와 같은 개 말초혈액 탐식세포의 탐식능에 있어 직접적인 억제효과를 나타내며, 또한 케타민 처리 단핵구세포로부터 생산되는 가용성인자에 의해서도 탐식세포의 탐식능이 억제되는 것으로 사료되었다.

Keywords

References

  1. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 1983; 79: 565-575 https://doi.org/10.1111/j.1476-5381.1983.tb11031.x
  2. Armstrong RA. Investigation of the inhibitory effects of $PGE_{2}$ and selective EP agonists on chemotaxis of human neutrophils. Br J Pharmacol 1995; 116: 2903-2908 https://doi.org/10.1111/j.1476-5381.1995.tb15943.x
  3. Aronoff DM, Canetti C, Peters-Golden M. Prostaglandin $E_{2}$ inhibits alveolar macrophage phagocytosis through an E-prostanoid 2 receptor-mediated increase in intracellular cyclic AMP. J Immunol 2004; 173: 559-565 https://doi.org/10.4049/jimmunol.173.1.559
  4. Boyaka PN, McGhee JR. Cytokines as adjuvants for the induction of mucosal immunity. Adv Drug Deliv Rev 2001; 51: 71-79 https://doi.org/10.1016/S0169-409X(01)00170-3
  5. Chang Y, Chen TL, Sheu JR, Chen RM. Suppressive effects of ketamine on macrophage functions. Toxicol Appl Pharmacol 2005; 204: 27-35 https://doi.org/10.1016/j.taap.2004.08.011
  6. Domino EF, Zsigmond EK, Domino LE, Domino KE, Kothary SP, Domino SE. Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay. Anesth Analg 1982; 61: 87-92
  7. Fredholm BB. Purines and neutrophil leukocytes. Gen Pharmacol 1997; 28: 345-350 https://doi.org/10.1016/S0306-3623(96)00169-3
  8. Grant IS, Nimmo WS, McNicol LR, Clements JA. Ketamine disposition in children and adults. Br J Anaesth 1983; 55: 1107-1111 https://doi.org/10.1093/bja/55.11.1107
  9. Hofbauer R, Moser D, Hammerschmidt V, Kapiotis S, Frass M. Ketamine significantly reduces the migration of leukocytes through endothelial cell monolayers. Crit Care Med 1998; 26: 1545-1549 https://doi.org/10.1097/00003246-199809000-00022
  10. Kanai AJ, Pearce LL, Clemens PR, Birder LA, VanBibber MM, Choi SY, de Groat WC, Peterson J. Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 2001; 98: 14126-14131 https://doi.org/10.1073/pnas.241380298
  11. Kawasaki T, Ogata M, Kawasaki C, Ogata J, Inoue Y, Shigematsu A. Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro. Anesth Analg 1999; 89: 665-669 https://doi.org/10.1097/00000539-199909000-00024
  12. Kim MJ, Kang JH, Yang MP. Effect of ketamine on the oxidative burst activity of canine peripheral blood leukocytes in vitro. J Vet Clin 2006; 23: 393-399
  13. Lammas DA, Stober C, Harvey CJ, Kendrick N, Panchalingam S, Kumararatne DS. ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. Immunity 1997; 7: 433-444 https://doi.org/10.1016/S1074-7613(00)80364-7
  14. McLeish KR, Stelzer GT, Wallace JH. Regulation of oxygen radical release from murine peritoneal macrophages by pharmacologic doses of PGE2. Free Radic Biol Med 1987; 3: 15-20 https://doi.org/10.1016/0891-5849(87)90034-7
  15. Mullen PG, Windsor AC, Walsh CJ, Fowler AA 3rd, Sugerman HJ. Tumor necrosis factor-alpha and interleukin-6 selectively regulate neutrophil function in vitro. J Surg Res 1995; 58: 124-130 https://doi.org/10.1006/jsre.1995.1020
  16. Nicholls DG. Mitochondrial membrane potential and aging. Aging Cell 2004; 3: 35-40 https://doi.org/10.1111/j.1474-9728.2003.00079.x
  17. Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, Niwa Y. The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions. Anesth Analg 1998; 86: 159-165 https://doi.org/10.1097/00000539-199801000-00032
  18. Schmidt H, Ebeling D, Bauer H, Bach A, Bohrer H, Gebhard MM, Martin E. Ketamine attenuates endotoxininduced leukocyte adherence in rat mesenteric venules. Crit Care Med 1995; 23: 2008-2014 https://doi.org/10.1097/00003246-199512000-00009
  19. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995; 13: 251-276 https://doi.org/10.1146/annurev.iy.13.040195.001343
  20. Underhill DM, Ozinsky A. Phagocytosis of microbes: complexity in action. Annu Rev Immunol 2002; 20: 825-852 https://doi.org/10.1146/annurev.immunol.20.103001.114744
  21. Yu Y, Zhou Z, Xu J, Liu Z, Wang Y. Ketamine reduces NFkappaB activation and TNFalpha production in rat mononuclear cells induced by lipopolysaccharide in vitro. Ann Clin Lab Sci 2002; 32: 292-298
  22. Zahler S, Heindl B, Becker BF. Ketamine does not inhibit inflammatory responses of cultured human endothelial cells but reduces chemotactic activation of neutrophils. Acta Anaesthesiol Scand 1999; 43: 1011-1016 https://doi.org/10.1034/j.1399-6576.1999.431007.x