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LEVAMISOLE AND FUNCTIONS OF PERITONEAL MACROPHAGES
798 normal response of the gallbladder to a fatty meal. While showing P.G.E2 to be an ineffective substitute for the fatty meal in cholecystography, our experience also indicates that P.G.E2 should not cause additional side-effects in patients with gallbladder disease. Department of Diagnostic Radiology University Central Hospital, Turku, Finland.
M. KORMANO* K. KATEVUO.
LEVAMISOLE AND FUNCTIONS OF PERITONEAL MACROPHAGES SIR,-According to the evidence partly discussed in your editorial of Jan. 18 (p. 151), the effect of levamisole on phagocytosis by macrophages has not been definitely established. Furthermore, investigations of the possible effect of this drug on intracellular killing of microorganisms, a host resistance mechanism equally as important as phagocytosis, have not yet been reported. We therefore studied the effect of levamisole on both functions in murine macrophages. S.P.F. mice (Central Institute for Breeding Laboratory Animals TNO, Austerlitz, Netherlands) were given daily subcutaneous injections of 5 mg. per kg. levamisole (donated by
Fig. 1-Effect of subcutaneous levamisole (5 mg./kg. daily) on rate of ingestion of Staph. albus by mice peritoneal macrophages (each curve represents mean of 2 experiments).
EFFECT OF LEVAMISOLE ON PHAGOCYTOSIS BY MOUSE PERITONEAL
MACROPHAGESf
t Mean of at least 3 experiments. t1 hour after incubation of 1-2 x 10. peritoneal macrophages, which are adherent to a glass coverslip, with 1-2 x 10’’ Staph. albus. § 3 minutes after an intraperitoneal injection of 1-2 x 10. Staph. albus.
Janssen Pharmaceutica, Beerse, Belgium) for 1 or for 5 days. All the work was done on mouse peritoneal macrophages obtained by washout with saline without prior intraperitoneal injection of an eliciting substance. The techniques for harvesting peritoneal macrophages, for the study of in-vitro phagocytosis by macrophages attached to a glass surface or in suspension, and for the in-vivo phagocytosis after intraperitoneal injection of microorganisms have been described.1-3 The results in the accompanying table show that, for phagocytosis in vitro, after 1 day’s treatment with levamisole the percentage of peritoneal macrophages ingesting Staphylococcus albus (p < 0001) and the mean number of ingested bacteria per macrophage (0-01 < P < 0.02) are both very significantly increased. However, after 5 days’ treatment the small increase in the percentage of macrophages containing bacteria just reaches statistical significance (p==0’05); the mean number of bacteria per phagocytosing macrophage is the same as in untreated animals. The addition of 100 {J.g. per ml. levamisole to the culture medium did not alter the percentage of macrophages ingesting bacteria. This observation prompted us to study the effect of this drug on in-vivo phagocytosis, but no difference was found (see table). To reach a more definite conclusion, we studied the effect on the kinetics of phagocytosis with a microbiological assay.3 The results show that the rate of ingestion of Staph. albus is not *
Present address: Department of Radiology, School of Medicine, Rochester, N.Y. 1. 2. 3.
University of Rochester
Furth, R., Cohn, Z. A. J. exp. Med. 1968, 128, 415. van Furth, R., Hirsch, J. G., Fedorko, M. E. ibid. 1970, 132, 794. van Furth, R., van Zwet, T. L. in Handbook of Experimental Immunology (edited by D. M. Weir); chap. 36. Oxford, 1973. van
Fig. 2-Effect of subcutaneous levamisole (5 mg./kg. daily) on intracellular killing by mice peritoneal macrophages (each curve represents mean of 2 experiments).
by 1 060) (fig. 1).
increased
or
5
We thus failed
days’ to
treatment
with levamisole (0-70 >p>
confirm earlier reports of enhanced
phagocytosis by macrophages in vitro4 or increased in-vivo uptake of substances by mononuclear phagocytes.5,6 It was also relevant to know whether, despite the absence of effect on the rate of phagocytosis, the microbicidal activity of macrophages is influenced by levamisole. A study in which intracellular killing by peritoneal macrophages, harvested 3 minutes after an intraperitoneal injection of 1-2 x 106 Staph. albus, was determined 3 showed that levamisole does not increase the rate of intracellular killing (0.4 > P > 0-30) (fig. 2). These findings lead to the conclusion that, in mice treated with levamisole for 5 days, phagocytosis and intracellular killing by non-elicited peritoneal macrophages is not- enhanced. Department of Microbial Diseases, University Hospital, Leiden, Netherlands.
G. VERSIJP THEDA L. VAN ZWET R. VAN FURTH.
4. Lima, A. O., Javierre, M. Ch., da Silva, W. D.,
Camara, D. S. Experientia, 1974, 30, 945. 5. Hoebeke J., Franchi, A. J. J. reticuloend. Soc. 1973, 14, 317. 6. Verhaegen, H., de Cree, J., de Cock, W., Verbruggen, F. New Engl. J. Med. 1973, 289, 1148.
M. KORMANO* K. KATEVUO.
LEVAMISOLE AND FUNCTIONS OF PERITONEAL MACROPHAGES SIR,-According to the evidence partly discussed in your editorial of Jan. 18 (p. 151), the effect of levamisole on phagocytosis by macrophages has not been definitely established. Furthermore, investigations of the possible effect of this drug on intracellular killing of microorganisms, a host resistance mechanism equally as important as phagocytosis, have not yet been reported. We therefore studied the effect of levamisole on both functions in murine macrophages. S.P.F. mice (Central Institute for Breeding Laboratory Animals TNO, Austerlitz, Netherlands) were given daily subcutaneous injections of 5 mg. per kg. levamisole (donated by
Fig. 1-Effect of subcutaneous levamisole (5 mg./kg. daily) on rate of ingestion of Staph. albus by mice peritoneal macrophages (each curve represents mean of 2 experiments).
EFFECT OF LEVAMISOLE ON PHAGOCYTOSIS BY MOUSE PERITONEAL
MACROPHAGESf
t Mean of at least 3 experiments. t1 hour after incubation of 1-2 x 10. peritoneal macrophages, which are adherent to a glass coverslip, with 1-2 x 10’’ Staph. albus. § 3 minutes after an intraperitoneal injection of 1-2 x 10. Staph. albus.
Janssen Pharmaceutica, Beerse, Belgium) for 1 or for 5 days. All the work was done on mouse peritoneal macrophages obtained by washout with saline without prior intraperitoneal injection of an eliciting substance. The techniques for harvesting peritoneal macrophages, for the study of in-vitro phagocytosis by macrophages attached to a glass surface or in suspension, and for the in-vivo phagocytosis after intraperitoneal injection of microorganisms have been described.1-3 The results in the accompanying table show that, for phagocytosis in vitro, after 1 day’s treatment with levamisole the percentage of peritoneal macrophages ingesting Staphylococcus albus (p < 0001) and the mean number of ingested bacteria per macrophage (0-01 < P < 0.02) are both very significantly increased. However, after 5 days’ treatment the small increase in the percentage of macrophages containing bacteria just reaches statistical significance (p==0’05); the mean number of bacteria per phagocytosing macrophage is the same as in untreated animals. The addition of 100 {J.g. per ml. levamisole to the culture medium did not alter the percentage of macrophages ingesting bacteria. This observation prompted us to study the effect of this drug on in-vivo phagocytosis, but no difference was found (see table). To reach a more definite conclusion, we studied the effect on the kinetics of phagocytosis with a microbiological assay.3 The results show that the rate of ingestion of Staph. albus is not *
Present address: Department of Radiology, School of Medicine, Rochester, N.Y. 1. 2. 3.
University of Rochester
Furth, R., Cohn, Z. A. J. exp. Med. 1968, 128, 415. van Furth, R., Hirsch, J. G., Fedorko, M. E. ibid. 1970, 132, 794. van Furth, R., van Zwet, T. L. in Handbook of Experimental Immunology (edited by D. M. Weir); chap. 36. Oxford, 1973. van
Fig. 2-Effect of subcutaneous levamisole (5 mg./kg. daily) on intracellular killing by mice peritoneal macrophages (each curve represents mean of 2 experiments).
by 1 060) (fig. 1).
increased
or
5
We thus failed
days’ to
treatment
with levamisole (0-70 >p>
confirm earlier reports of enhanced
phagocytosis by macrophages in vitro4 or increased in-vivo uptake of substances by mononuclear phagocytes.5,6 It was also relevant to know whether, despite the absence of effect on the rate of phagocytosis, the microbicidal activity of macrophages is influenced by levamisole. A study in which intracellular killing by peritoneal macrophages, harvested 3 minutes after an intraperitoneal injection of 1-2 x 106 Staph. albus, was determined 3 showed that levamisole does not increase the rate of intracellular killing (0.4 > P > 0-30) (fig. 2). These findings lead to the conclusion that, in mice treated with levamisole for 5 days, phagocytosis and intracellular killing by non-elicited peritoneal macrophages is not- enhanced. Department of Microbial Diseases, University Hospital, Leiden, Netherlands.
G. VERSIJP THEDA L. VAN ZWET R. VAN FURTH.
4. Lima, A. O., Javierre, M. Ch., da Silva, W. D.,
Camara, D. S. Experientia, 1974, 30, 945. 5. Hoebeke J., Franchi, A. J. J. reticuloend. Soc. 1973, 14, 317. 6. Verhaegen, H., de Cree, J., de Cock, W., Verbruggen, F. New Engl. J. Med. 1973, 289, 1148.