Impaired function of postoperative macrophages from zinc-deficient rats decreases collagen contraction
Corresponding Author
M. REZA Ghassemifar
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Faculty of Health Science, Department of Pathology II, S-581 85 Linköping, Sweden.Search for more papers by this authorMIKAEL G. Olsson
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Search for more papers by this authorMAGNUS S. ÅGren
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Search for more papers by this authorLENNART E. FranzÉN
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Search for more papers by this authorCorresponding Author
M. REZA Ghassemifar
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Faculty of Health Science, Department of Pathology II, S-581 85 Linköping, Sweden.Search for more papers by this authorMIKAEL G. Olsson
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Search for more papers by this authorMAGNUS S. ÅGren
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Search for more papers by this authorLENNART E. FranzÉN
Faculty of Health Science, Department of Pathology II, Linköping, Sweden
Search for more papers by this authorAbstract
Zinc deficiency impairs connective tissue contraction in the perforated rat mesentery model. Since the rat mesentery is almost avascular, free peritoneal macrophages are important for mesenteric repair. Impairment of contraction may thus be caused either by a direct effect of zinc deficiency on tissue cells or by hampered macrophage function. To further elucidate the role of macrophages in tissue contraction, we studied their effect on lattice contraction. A number of typical functions of macrophages in zinc deficiency were also investigated. Lattice contraction was significantly impaired by conditioned medium from zinc-deficient macrophages. Zinc deficiency did not influence peripheral blood leukocyte number, but postoperatively the number of peritoneal macrophages increased on days 7 and 10. A significant release of lysosomal enzymes from macrophages was recorded during phagocytosis, whilst no difference was observed between controls and zinc-deficient macrophages. Superoxide anion generation during phagocytosis was not significantly increased in zinc deficiency. Conditioned medium from zinc-deficient macrophages was shown to impair lattice contraction in vitro and the results are compatible with impaired macrophage function as a cause of decreased connective tissue contraction in vivo.
REFERENCES
- 1 Allen, J. I., Perri, R. T., Mcclain, C. J. & Kay, N. E. Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. J. Lab. Clin. Med. 102: 577–589, 1983.
- 2 Bell, E., Ivarsson, B. & Merrill, C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci. USA. 76: 1274–1278, 1979.
- 3 Bray, T. M. & Bettger, W. J.: The physiological role of zinc as an antioxidant. Free Radic. Biol. Med. 8(3): 281–291, 1990.
- 4 Chvapil, M. Effect of zinc on cells and biomem-branes. Med. Clin. N. Am. 60: 799–812, 1976.
- 5 Chvapil, M., Stankova, L., Bartos, Z., Cox, T. & Nichols, W. Mobility of peritoneal inflammatory cells after in vivo supplementation with zinc. J. Reticuloendothel. Soc. 25: 345–350, 1979.
- 6 Chvapil, M., Stankova, L., Bernhard, D. S., Weldy, P. L., Calson, E. C. & Campbell, J. B. Effect of zinc on peritoneal macrophages in vitro. Infect. Immun. 16: 367–373, 1977.
- 7 Davies, P. & Allison, A. Secretion of macrophage enzymes in relation to the pathogenesis of chronic inflammation. In: D. S. Nelson (Ed.): Immunology of the macrophage. Academic Press 1976, pp. 427-461.
- 8 Ehrlich, H. P. & Rajaratnam, J. B. M. Cell locomotion forces versus cell contraction forces for collagen lattice contraction: An in vitro model of wound contraction. Tissue Cell 22 (4): 407–417, 1990.
- 9 Ercan, M. T. & Bor, N. M.: Phagocytosis by macrophages in zinc-deficient rats. Int. J. Rad. Appl. Instrum. B 18 (7): 765–768, 1991.
- 10 FranzÉN, L. & Ghassemifar, R. Connective tissue repair in zinc deficiency. An ultrastructural morphometry study in perforated mesentery in rats. Eur. J. Surg. 158: 333–337, 1992.
- 11 FranzÉN, L., Malcherek, P. & Agren, M. Scar tissue formation and angiogenesis during connective tissue repair in zinc deficiency. Wounds 2: 170–177, 1990.
- 12 FranzÉN, L. & Norrby, K. A tissue model for quantitative studies on time course of healing, rate of healing, and cell proliferation after wounding. Acta path, microbiol. immunol. scand. Sect. A. 91: 281–289, 1983.
- 13 FranzÉN, L. & ÅGren, M. Effect of zinc deficiency on connective tissue repair in the perforated rat mesentery. J. Trace Elem. Exp. Med. 4: 37–49, 1991.
- 14 FranzÉN, L. E. & Roberg, K. Impaired connective tissue repair in streptozotocin-diabetes shows ultrastructural signs of impaired contraction. J. Surg. Res. 1994, in press.
- 15 Gupta, R. P., Verma, P. C. & Gupta, R. K. P. Experimental zinc deficiency in guinea-pigs: clinical signs and some haematological studies. Br. J. Nutr. 54: 421–428, 1985.
- 16 Knighton, D. R. & Fiegel, V. D. The macrophages: Effector cell wound repair. Prog. Clin. Biol. Res. 299: 217–226, 1989.
- 17 Leaback, D. H. & Walker, P. G. Studies on glu-cosaminidase. 4. The fluorimetric assay of Nacetyl-β-glucosaminidase. Biochem. J. 78: 151–156, 1961.
- 18 Lehman, E. L. Nonparametrics. Statistical methods based on ranks. Holden-Day Inc., San Francisco 1975.
- 19 Leibovich, S. J. & Ross, R. The role of the macrophage in wound repair. Am. J. Pathol. 78: 71–91, 1975.
- 20 Leoni, P., Dean, R. T. & Jessup, W. Secretion of hydrolases by mononuclear phagocytes. In: R. T. Dean & W. Jessup (Eds.): Mononuclear phagocytes. Elsevier 1985, pp. 181-202.
- 21 Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. Protein measurement with the fol-in phenol reagent. J. Biol. Chem. 193: 265–270, 1951.
- 22 Malcherek, P. & FranzÉN, L. A new model for the study of angiogenesis in connective tissue repair. Microvasc. Res. 42: 217–223, 1991.
- 23 MorliÉRe, P., Reyftmann, J. P., Kohen, C., Kohen, E., Santus, R. & Dubertret, L. Study of lysosomal enzyme release by microspectrofluorometry on single cells. Br. J. Dermatol. 111(Suppl. 27): 235–238, 1984.
- 24 Oberleas, D., Seymour, J. K., Lenaghan, R., Hovanesicm, J., Wilson, R. F. & Prasad, A. S. Effect of zinc deficiency on wound healing in rats. Am. J. Surg. 121: 566–568, 1971.
- 25 Olsson, G. M., Brunmark, A. & Brunk, U. T. Acridine orange-mediated photodamage of microsomal- and lysosomal fractions. Virchows Arch. B 56: 247–257, 1989.
- 26 Olsson, G. M., Roberg, K. & Rundqvist, I. The use of acridine orange cytofluorometry in the study of macrophage lysosomal exocytosis. Anal. Cell. Pathol. 2: 179–188, 1990.
- 27 Rahmat, A., Norman, J. N. & Smith, G. The effect of zinc deficiency on wound healing. Br. J. Surg. 61: 271–273, 1974.
- 28 Rappolee, D. A. & Werb, Z. Macrophage-derived growth factors. In: Current topics in microbiology and immunology. Springer-Verlag 1992, pp. 87-126.
- 29 Sandslead, H. H., Lanier, V. C., Shepard, G. H. & Gillespie, D. D.: Zinc and wound healing: Effects of zinc deficiency and zinc supplementation. Am. J. Clin. Nutr. 23: 514–519, 1970.
- 30 Schnyder, J. & Baggiolini, M. Secretion of lysosomal hydrolases by stimulated and nonstimulated macrophages. J. Exp. Med. 148: 435–450, 1978.
- 31 Weiss, S. J., King, G. W. & Lobuglio, A. F. Superoxide generation by human monocytes and macrophages. Am. J. Hematol. 4: 1–8, 1978.
- 32 Weissmann, G., Zurier, R. B., Spieler, P. J. & Goldstein, I. M. Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles. J. Exp. Med. 134: 149–165, 1971.
- 33 White, M. J. & Heckler, F. R. Oxygen free radicals and wound healing. Clin. Plast. Surg. 17: 473–484, 1990.
- 34 Wiernik, A., Johansson, A., Jarstrand, C. & Camner, P. Rabbit lung after inhalation of soluble nickel. 1. Effects on alveolar macrophages. Environ. Res. 30: 129–141, 1983.
- 35 Wirth, J. J., Fraker, P. J. & Kierszenbaum, F. Changes in the levels of marker expression by mononuclear phagocytes in zinc-deficient mice. J. Nutr. 114: 1826–1833, 1984.
- 36 Wirth, J. J., Fraker, P. J. & Kierszenbaum, F. Zinc requirement for macrophage function: effect of zinc deficiency on uptake and killing of a protozoan parasite. Immunology 68: 114–119, 1989.
- 37 ÅGren, M. S. & FranzÉN, L. Influence of zinc deficiency on breaking strength of 3-week-old skin incisions in the rat. Acta Chir. Scand. 156: 667–670, 1990.