Key words: systemic lupus erythematosus (SLE), monocyte, priming effect, polymorphnuclear neutrophils-chemiluminescence corticosteroid

Transcription

1 Key words: systemic lupus erythematosus (SLE), monocyte, priming effect, polymorphnuclear neutrophils-chemiluminescence corticosteroid (PMN-CL),

2 Table 1 Patient profiles PSL: prednisolone,*: duration of therapy after prednisolone-dose up

3 Fig. 1 Effects of preincubation of neutrophils in monocyte culture supernatant (MS) on PMN-CL. Purified monocytes from normal controls (n=10) were cultured. Supernatants were harvested 6hr after addition of LPS. FMLP induced PMN-CL was assayed after incubation of neutrophils for 15min in the resultant supernatant. NC: control medium, LPS (-): MS without adding LPS, LPS (+): MS with adding LPS. Fig. 2 In vitro effects of dexamethasone treated monocyte supernatant (MS) on PMN-CL. Purified monocytes from normal controls (n=3) were incubated for 24hr in medium with or without dexamethasone (licg/ml) prior to exposure to LPS for 6hr. Supernatants were harveted and assayed. cont: control medium, dex (-): MS without adding dexamethasone, dex (+): MS with adding dexamethasone.

4 Fig. 3 Effects of preincubation of neutrophils in T lymphocyte culture supernatant (TS) on PMN- CL. Purified T lymphocytes from normal controls (n=3) were cultrued for 24hr after addition of PHA in medium with or without dexamethasone (1ug/ml). cont: control medium, dex (-): TS without dexamethasone, dex(+): TS with dexamethasone. Fig. 4 Effects of preincubation of neutrophils in recombinant human (rh) TNF or rhil-1Ĉ on PMN-CL. FMLP-induced PMN-CL was assyed after incubation of neutrophils for 15min in rhtnf or rhil-1.

5 Fig. 5 Comparision of enhancing effects of monocyte culture supernatant on PMN-CL between normal controls and collagen disease patients. Monocyte supernatants (MS) were harvested 6hr after addition of LPS. Stimulation index=(pmn-cl preincubated in monocyte supernatant)/ (PMN-CL preincubated in control medium), NC: MS from normal controls, steroid (+): MS from patients under steroid therapy, steroid (-): MS from patients before steroid therapy. Fig. 6 The ratios of stimulation indexs of collagen disease patients to those of normal controls. steroid(4-) : patients under steroid therapy, steroid(-): patients before steroid therapy.

6 1) Ferrante, A., Nandoskar, M., Bates, E. J. & Goh, D. H. B.: Staphylococcus aureusstimulated human mononuclear leucocyteconditioned medium augments the basal and stimuli-induced neutrophil respiratory burst and degranulation. Immunol., 60: , ) Shalaby, M. R., Aggarwal, B. B., Rinderknecht, E., Svedersky, L. P., Finkle, B. S. & Palladino, M. A. Jr.: Activation of human polymorphonuclear neutrophil functions by interferony and tumor necrosis factors. J. Immunol., 135: , ) Klebanoff, S. J., Vadas, M. A., Harlan, J.M., Sparks, L.H., Gamble, J. R., Agosti, J.M. & Waltersdorph, A. M.: Stimulation of neutrophils by tumor necrosis factor. J. Immunol., 136: , ) Larrick, J. W., Graham, D., Toy, K., Lin, L. S., Senyk, G. & Fendly, B. M.: Recombinant tumor necrosis factor causes activation of human granulocytes. Blood, 69: , ) Atkinson, Y. H., Marasco, W. A., Lopez, A.F. & Vadas, M. A.: Recombinant human necrosis factor-a. J. Clin. Invest., 81: , ) Ferrante, A., Nandoskar, M., Bates, E.J., Goh, D. H. B. & Beard, I.J. Tumor necrosis factor beta (lymphotoxin) inhibits locomotion and stimulates the respiratory burst and degranulation of neutrophils. Immunol., 63: , ) Kowanko, I. C.& Ferrante, A.: Stimulation of neutrophil respiratory burst and lysosomal enzyme release by human interferon-gamma. Immunol., 62: , ) Cassatella, M. A., Cappelli, R., Bianca, V. D., Grzeskowiak, M., Dusi, S. & Berton, G.: Interferon-gamma activates human neutrophil oxygen metabolism and exocytosis. Immunol., 63 : , ) Berkow, R. L. & Dodson, M. R.: Biochemical mechanisms involved in the priming of neutrophils by tumor necrosis factor. J. Leukocyte. Biol., 44: , ) Kharazmi, A., Nielsen, H. & Bendtzen, K.: Recombinant Interleukin la andĈ prime human monocyte superoxide production but have no effect on chemotaxis and oxidative burst responce of neutrophils. Immunobiol., 177: 32-39, ) Blanchard, D. K., Djeu, J. Y., Klein, T. W., Friedman, H. & Stewart W. E. II : Protective effects of tumor necrosis fator in experimental legionella pneumophila infections of mice via activation of PMN function. J. Leukocyte.

7 Biol., 43: , ) Staples, P.J., Gerding, D. N., Decker, J. L.& Gordon, R. S. Jr.: Incidence of infections in systemic lupus erythrmatosus. Arthritis. Theum., 17: 1-10, ) Ginzler, E., Diamond, H., Kaplan, D., Weiner, M., Schlesinger, M. & Seleznick, M.: Computer analysis of factors infuencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum., 21: 37-44, ) Brandt, L. & Hedberg, H.: Impaired phagocytosis by peripheral granulocytes in systemic lupus erythematosus. J. Haematol., 6: , ) Zurier, R. B.: Reduction of phagocytosis and lysosomal enzyme release from leukocyte by serum from patient with systemic lupus eryth- 17) Waage, A.& Bakke, O.: Glucocorticoids suppress the production of tumor necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunol., 63: , ) Katayama, S., Chia, D., Knutson, D. W. & Barnett, E. V.: Decreased Fc receptor avidity and degenerative function of monocytes from patients with systemic lupus erythematosus. J. Immunol., 131: , ) Baba, T., Ochiya, T., Baba, A., Yaoita, H.& Uyeno, K.: An inhibitory factor aginst monocyte spreading in the sera of patients with systemic lupus erythemat-osus. Biol., 38: , J. Leukocyte 20) Shirakawa, F., Yamashita, U.& Suzuki, H.: ematosus. Arthritis Rheum., 19: 73-78, Reduced function of HLA-DR-positive monocyte in patient with systemic lupus erythematosus. J. Clin. Immunol., 5: , A Study of Enhancing Effects of Monocyte Culture Supernatant on Polymorphonuclear Neutrophils-Chemiluminescence Comparison between Normal Controls and Collagen Disease Patients Yoshinori SHIMATSU, Kenichi IKARASHI, Masaaki NAKANO, Koichi WADA, Masatoshi NIWAYAMA & Masaaki ARAKAWA Department of Medicine (II), Niigata University Medical School, Niigata, Japan Priming effect of monocyte culture supernatant on polymorphonuclear neutrophils (PMN)- chemiluminescence (CL) was studied in patients with systemic lupus erythematosus (n=11) and mixed connective tissue disease (n=4). In normal controls, N-formyl-methionyl-leucyl-penylalanine (FMLP) induced PMN-CL was enhanced when PMN were previously incubated for 15 minutes with monocyte culture supernatant (MS) or T lymphocyte culture supernatant (TS) or T lymphocyte culture supernatant (TS). The enhancing effect of MS on PMN-CL was greater than that of TS. This enhancing effect of MS was inhibited by adding of dexamethasone (1ug/ml) during the culture. Recombinant human TNF also enhanced PMN-CL as well as MS. When compared the enhancing effects of MS between patients and normal controls, that of patients under corticosteroid therapy (average predonisolone dose 39.5 mg/day) was reduced significantly. Thus, we concluded that the cytokines from monocyte contributed PMN phagocytosis of invading microorganisms, and that this monocyte-mediated PMN phagocytosis was suppressed partly by corticosteroids in collagen disease.