Clin. exp. Immunol. (1990) 80, 373-375
Polyamine oxidase activity in rheumatoid arthritis synovial fluid A. FERRANTE, R. J. STORER & L. J. CLELAND* Department of Immunology and University Department of Paediatrics, Adelaide Children's Hospital, and * Department of Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia
(Acceptedfor publication 1 December 1989)
SUMMARY Oxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity
Keywords polyamine oxidases rheumatoid arthritis
INTRODUCTION
MATERIALS AND METHODS
Polyamine oxidases (PAO) have been tentatively defined as amine oxidases capable of catalysing the oxidation of the polyamines spermine and spermidine (Morgan, 1985a, 1989). In non-ruminants the enzymes are not usually detectable in the blood. However, significant levels may be found during infecp tion, in 'pregnancy serum,' retroplacental serum and macro phages (Gaugas & Curzen, 1978; Morgan, Ferluga & Allisoi', 1980; Illei & Royston, 1983; Morgan, 1985b). These enzymes react with polyamines and generate highly reactive aminoaldehydes (Fig. 1), which have been shown to mediate intraerythrocyte death of malarial parasites (Morgan, Christensen & Allison 1981; Ferrante, Rzepczyk & Allison 1983; Rzepczyk, Saul & Ferrante 1984; Morgan et al., 1986; Egan et al., 1986), lysis of trypanosomes (Ferrante, Allison & Hirumi, 1982; Ferrante, Rzepczyk & Saul, 1984), killing of various helminth parasites (Ferrante et al., 1986a), lysis of tumour cells (Storer et al., 1988; Bachrach, Abzug & Bekierkurst, 1967), inhibition of lymphocyte proliferation (Byrd, Jabobs & Amos, 1977; Allen et al., 1979; Gaugas, 1980; Hussain, Smith & Allen, 1983) and inhibition of neutrophil oxygen radical production and chemotaxis (Ferrante, 1985; Ferrante et al., 1986b). Because of their effects on inflammatory cells such as neutrophils, it was postulated (Ferrante 1985; Ferrante et al., 1986b) that the antiinflammatory activity found in inflammatory exudates such as synovial fluid from rheumatoid arthritis patients (Capstick, Lewis & Cosh, 1975) may be explained in part by the presence of polyamine oxidizing enzymes. We now present evidence that PAO are present in synovial fluids from patients with rheumatoid arthritis. Correspondence: Dr A. Ferrante, Department of Immunology, Adelaide Children's Hospital, North Adelaide, South Australia 5006.
Polyamines
'4C-spermine tetrahydrochloride (N, N'-bis-(3-aminopropyl)14C-tetramethylene- 1,4-diamine) was obtained from Amersham Laboratories (Amersham, UK). 3H-spermidine trihydrochloride (N-(3-aminopropyl) -1, 4-tetramethylene- 1, 4-diamine), [terminal methylenes 3H(N)] was from du Pont de Nemours & Co. (Boston, MA). Spermine tetrahydrochloride and spermidine trihydrochloride were from Sigma Chemical Co. (St Louis,
MO).
14C-spermine oxidation assay method PAO activity was measured using the radiochemical method described by Morgan & Illei (1980b) with minor modifications. Briefly, 100 ,ul of sample were added to 200 pl 0 05 M Tris-HCI buffered spermine (46-6 kBq/pmol; 303 gM) plus 0-1% Triton X100 (v/v), pH 7-4 at 37°C. The reaction mixture was incubated in a 37 0 + 0l1C water bath for 90 min after which the reaction was
NH2(CH2)3N H (CH2)4N H (CH2)3N H2+02+ H20-+ spermine
NH2(CH2)3NH(CH2)4+ spermidine
NH2(CH2)2CHO+H202 3-amino-propionaldehyde
NH2(CH2)3 NH(CH2)4 NH2+02+H20-+ spermidine
NH2(CH2)2CHO+ 3-amino-porpionaldehyde
NH2(CH2)4NH2+H202 Putrescine
Fig. 1. The oxidation of polyamines by human polyamine oxidases.
373
374
A. Ferrante, R. J. Storer & L. J. Cleland Table 1. Polyamine oxidase activity in synovial fluids from rheumatoid arthritis patients
Fluid Serum type RA synovial fluid (n = 12)* RA serum (n = 6)* Retroplacental serum (n = 58) Pooled human serum 'Control' synovial fluid (n = 3)
Enzyme activity (mU/i) (m + s.e.m.) 490 +44 89+ 36 1,722 + 114 116 144-9 +4-0
Synovial fluid or serum from rheumatoid arthritis (RA) patients. *
stopped by the addition of 50 pl trichloroacetic acid (50% w/v), precipitated protein was sedimented by centrifugation. Reaction products and substrate were separated by step-wise elution with hydrochloric acid 1-9 M (10 ml) and 4-0 M (10 ml) on Dowex 50W-X2, 200-400 mesh (BioRad laboratories, Richmond, CA) cation exchange resin (0-8 x 4 cm). Aliquots (200 pl) of the reaction mixture supernatant were applied to the columns followed by 200 p1 deionized water. The eluates were collected into polypropylene tubes, aliquots of each fraction were transferred to scintillation vials amd mixed with scintillation cocktail (Beckman Ready-solv EP). For each sample d/min was determined by counting in a Mark III liquid scintillation counter (Searle Analytic, Des Plains, TO) and percent substrate conversion calculated. Controls and blanks were included in each assay. The separation of substrate and reaction products by this method was confirmed using 3H-spermidine and '4C-spermine with dual-channel scintillation counting. Enzyme activity is expressed as international units (i.e. pmol product formed/min).
Retroplacental fluid Retroplacental fluid was collected from placentae after elective caesarean delivery at 38-40 weeks gestation as described by Klopper & Hughes (1978). Serous blood stained fluid was obtained from the maternal surface of the placenta. This fluid, which is mainly intervillous blood plus decidual and placental interstitial fluid, was allowed to clot for 30 min at 370C. The blood mixture was then centrifuged and the serum (termed retroplacental serum) was collected.
Synovialfluid Samples were obtained under local anaesthesia (xylocaine i.o.) from patients with definite or classical rheumatoid arthritis by ARA criteria classification (Mitchell & Fries, 1982) attending the Rheumatology Unit at the Royal Adelaide Hospital. Control synovial fluids were obtained at autopsy. RESULTS all 12 rheumatoid arthritis synovial that showed The results fluid samples examined were positive for PAO activity, ranging from 200 to 800 mU/l (Table 1). Only low activity was detected in 'control' synovial fluids, similar to levels found in normal serum and the serum from rheumatoid arthritis patients. However, the levels of activity in synovial fluids of rheumatoid arthritis patients were low compared to those of retroplacental serum (Table 1).
DISCUSSION These findings represent the first evidence that PAO are present in inflammatory exudates and it is possible that this enzyme(s) is part of the inflammation molecular complex which may be involved in tissue degradation and tissue regeneration in diseases such as rheumatoid arthritis. Polyamines are present in all tissues and their concentrations in tissue fluids significantly rise as a consequence of tissue damage and regeneration (Gaugas, 1980). The oxidation of these polyamines by PAO could contribute to the events occurring in various inflammatory sites. Their effects could range from stimulation and regulation of tissue cell growth to suppression of the leucocytic inflammation. PAO may be released from inflammatory macrophages and/or pannus tissue associated with affected joints of rheumatoid arthritis patients. The regulation of inflammation by PAO in disease such as rheumatoid arthritis is supported by the findings of Flescher et al. (1989), who obtained evidence suggesting that the polyamine-polyamine oxidase system is somehow involved in the down-regulation of immune reactivity associated with rheumatoid arthritis, in particular to a downregulation of interleukin-2 production. The levels of PAO levels of 500 mU/l found in rheumatoid arthritis synovial fluid would appear to be sufficient to inhibit lymphocyte proliferation, since Morgan & Illei (1980a) showed that inhibition of lymphocyte proliferation occurred as PAO activity exceeded 200 mU/l. The capacity of oxidized polyamines to inhibit the migration and oxygen radical production of neutrophils (Ferrante, 1985; Ferrante et al., 1986b) as well as cytokine production (Flescher et al., 1989) could explain the anti-inflammatory activity found in arthritic rat plasma (Persellin, 1972; Lewis, Capstick & Bers, 1976) and human rheumatoid synovial fluid (Capstick et al., 1975). REFERENCES ALLEN, J.C., SMITH, J.., HUSSAIN, J.M., THOMAS, J.M. & GAUGAS, J.M. (1979) Inhibition of lymphocyte proliferation by polyamines requiresruminant -plasma polyamine oxidase Eur. J. Biochem. 102, 153. BACHRACH, U., ABZUG, S. & BEKIERKURST, A. (1967) Cyctotoxic effect of oxidized spermine on Ehrlich ascites cells. Biochim. biophys. Acta, 134, 174. BYRD, W.J., JACOBS, D.M. & AMos, M.S. (1977) Synthetic polyamines added to cultures containing bovine sera reversibly inhibit in vitro parameters of immunity. Nature, 267, 621. CAPSTICK, R.B., LEWIS, D.A. & COSH, J.A. (1975) Naturally occurring factors in the synovial fluids of patients with rheumatic disease and their possible mode of action. Ann. rheum. Dis. 34, 213. EGAN, J.E., HAYNES, J.D., BROWN, N.D. & EISMANN, C.S. (1986) Polyamine oxidase in human retroplacental serum inhibits the growth of Plasmodium falciparum. Am. J. trop. Med. Hyg. 35, 890. FERRANTE, A. (1985) Inhibition of human neutrophil locomotion by the polyamine oxidase-polyamine system. Immunology, 54, 785. FERRANTE, A., ALLISON, A.C. & HIRUMI, H. (1982) Polyamine oxidasemediated killing of African trypanosomes. Parasite Immunol. 4, 349. FERRANTE, A., RZEPCZYK, C.M. & ALLISON, A.C. (1983) Polyamine oxidase mediated intraerythrocytic death of Plasmodiumfalciparum. Trans. R. Soc. trop. Med. Hyg. 77, 789. FERRANTE, A., RZEPCZYK, C.M. & SAUL, A.J. (1984) Polyamine oxidase-mediated trypanosome killing: the role of hydrogen peroxide and aldehydes. J. Immunol. 133, 2157. FERRANTE, A., LJUNGSTROM, I., RZEPCZYK, C.M. & MORGAN, D.M.L. (1986a) Differences in sensitivity of Schistosoma mansoni schistoso-
Polyamine oxidases in rheumatoid arthritis mula, Dirofilaria immitis microfilariae, and Nematospiroides dubius third-stage larvae to damage by the polyamine oxidase-polyamine system. Infect. Immun. 53, 606. FERRANTE, A., MAXWELL, G.M., RENCIS, V.0., ALLISON, A.C. & MORGAN D.M.L. (1986b) Inhibition of the respiratory burst of human neutrophils by the polyamine oxidase-polyamine system. Int. J. Immunopharmacol. 8, 411. FLESCHER, E.F., BOWLIN, T.L., BALLESTER, A., HOUK, R. & TALAL, N. (1989) Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis J. clin. Invest. 83, 1356. GAUGAS, J.M. (1980) Biogenic diamines and the polyamines in support and in inhibition of lymphocyte proliferation. In Polyamines in Biomedical Research (ed. by J. M. Gaugas) p. 343. John Wiley & Sons, Chichester. GAUGAS, J.M. & CURZEN, P. (1978) Polyamines interaction with pregnancy serum in suppression of lyphocyte transformation. Lancet, i, 18. HUSSAIN, J.I., SMITH, C.J. & ALLEN, J.C. (1983) Polyamine mediated inhibition of in vitro cell proliferation is not due to acrolein. Cell Tissue Kinet. 16, 583. KLOPPER, A. & HUGHES, G. (1978) Placental secretion of oestrogens and protein hormones. Arch. Gynaecol. 225, 171. LEWIS, D.A., CAPSTICK, R.B. & BEST, R. (1976) The control of rheumatic disease by endogenous protein. Biochem. Pharmacol. 25, 1435. MITCHELL, D.M. & FRIES, J.F. (1982) An analysis of the American rheumatism association criteria for rheumatoid arthritis. Arthritis Rheum. 25, 481. MORGAN, D.M.L. (1985a) Polyamine oxidases. Biochem. Soc. Trans. 13, 222. MORGAN, D.M.L. (1985b) Human pregnancy-associated polyamine oxidase:partial purification and properties. Biochem. Soc. Trans. 13, 351. MORGAN, D.M.L. (1989) Polyamine oxidases and oxidised polyamines.
375
In The Physiology of Polyamines Vol. 1. (ed. by U. Bachrach & Y. Heimer) p. 203, CRC press, Oxford. MORGAN, D.M.L. & ILLEI, G. (1980a) Polyamine-polyamine oxidase interaction: part of maternal protective mechanism against fetal rejection. Br. Med. J. 280,1295. MORGAN, D.M.L. & ILLEI, G. (1980b) Radiochemical estimation of serum polyamine oxidase activity in human pregnancy. Med. Lab. Sci. 38,49. MORGAN, D.M.L., CHRISTENSEN, J.R. & ALLISON, A.C. (1981) Polyamine oxidase and the killing of intracellular parasites. Biochem. Soc. Trans. 9, 563. MORGAN, D.M.L., FERLUGA, J. & ALLISON, A.C. (1980) Polyamine oxidase and macrophage function. In Polyamines in Biomedical Research (ed. by J. M. Gaugas) p. 303, John Wiley, Chichester. MORGAN, D.M.L., ILLEI, G. & ROYSTON, J.P. (1983) Serum polyamine oxidase activity in normal pregnancy. Br. J. Obstet. Gynaecol. 90,1194. MORGAN D.M.L., BACHRACH, U., ASSARAF, Y.G., HARARI, E. & GOLENSER, J. (1986) The effect of purified aminoaldehydes produced by polyamine oxidation on the development in vitro of Plasmodium falciparum in normal and glucose-6-phosphate-dehydrogenase-deficient erythrocytes. Biochem. J. 236, 97. PERSELLIN, R.A. (1972) Lysosome stabilization by adjuvant arthritis serum. Arthritis Rheum. 15, 44. RZEPCZYK, C.M., SAUL, A.J. & FERRANTE, A. (1984) Polyamine oxidase-mediated intraerythrocytic killing of Plasmodiumfalciparum: Evidence for the role of reactive oxygen metabolites. Infect. Immun. 43, 238. STORER, R.J., FERRANTE, A., BATES, D.J., ZOLA, H. & MORGAN D.M.L. (1988) Retroplacental polyamine oxidase: antimicrobial, antiinflamatory, antitumour and immunosuppressive properties further Characterization. In Placental and Endometrial Proteins: Basic and Clinical Aspects (ed. by Y. Tomoda, S. Mizutani, 0. Narita & A. Klopper), p. 349. VSP Science Press, Utrecht.
Polyamine oxidase activity in rheumatoid arthritis synovial fluid A. FERRANTE, R. J. STORER & L. J. CLELAND* Department of Immunology and University Department of Paediatrics, Adelaide Children's Hospital, and * Department of Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia
(Acceptedfor publication 1 December 1989)
SUMMARY Oxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity
Keywords polyamine oxidases rheumatoid arthritis
INTRODUCTION
MATERIALS AND METHODS
Polyamine oxidases (PAO) have been tentatively defined as amine oxidases capable of catalysing the oxidation of the polyamines spermine and spermidine (Morgan, 1985a, 1989). In non-ruminants the enzymes are not usually detectable in the blood. However, significant levels may be found during infecp tion, in 'pregnancy serum,' retroplacental serum and macro phages (Gaugas & Curzen, 1978; Morgan, Ferluga & Allisoi', 1980; Illei & Royston, 1983; Morgan, 1985b). These enzymes react with polyamines and generate highly reactive aminoaldehydes (Fig. 1), which have been shown to mediate intraerythrocyte death of malarial parasites (Morgan, Christensen & Allison 1981; Ferrante, Rzepczyk & Allison 1983; Rzepczyk, Saul & Ferrante 1984; Morgan et al., 1986; Egan et al., 1986), lysis of trypanosomes (Ferrante, Allison & Hirumi, 1982; Ferrante, Rzepczyk & Saul, 1984), killing of various helminth parasites (Ferrante et al., 1986a), lysis of tumour cells (Storer et al., 1988; Bachrach, Abzug & Bekierkurst, 1967), inhibition of lymphocyte proliferation (Byrd, Jabobs & Amos, 1977; Allen et al., 1979; Gaugas, 1980; Hussain, Smith & Allen, 1983) and inhibition of neutrophil oxygen radical production and chemotaxis (Ferrante, 1985; Ferrante et al., 1986b). Because of their effects on inflammatory cells such as neutrophils, it was postulated (Ferrante 1985; Ferrante et al., 1986b) that the antiinflammatory activity found in inflammatory exudates such as synovial fluid from rheumatoid arthritis patients (Capstick, Lewis & Cosh, 1975) may be explained in part by the presence of polyamine oxidizing enzymes. We now present evidence that PAO are present in synovial fluids from patients with rheumatoid arthritis. Correspondence: Dr A. Ferrante, Department of Immunology, Adelaide Children's Hospital, North Adelaide, South Australia 5006.
Polyamines
'4C-spermine tetrahydrochloride (N, N'-bis-(3-aminopropyl)14C-tetramethylene- 1,4-diamine) was obtained from Amersham Laboratories (Amersham, UK). 3H-spermidine trihydrochloride (N-(3-aminopropyl) -1, 4-tetramethylene- 1, 4-diamine), [terminal methylenes 3H(N)] was from du Pont de Nemours & Co. (Boston, MA). Spermine tetrahydrochloride and spermidine trihydrochloride were from Sigma Chemical Co. (St Louis,
MO).
14C-spermine oxidation assay method PAO activity was measured using the radiochemical method described by Morgan & Illei (1980b) with minor modifications. Briefly, 100 ,ul of sample were added to 200 pl 0 05 M Tris-HCI buffered spermine (46-6 kBq/pmol; 303 gM) plus 0-1% Triton X100 (v/v), pH 7-4 at 37°C. The reaction mixture was incubated in a 37 0 + 0l1C water bath for 90 min after which the reaction was
NH2(CH2)3N H (CH2)4N H (CH2)3N H2+02+ H20-+ spermine
NH2(CH2)3NH(CH2)4+ spermidine
NH2(CH2)2CHO+H202 3-amino-propionaldehyde
NH2(CH2)3 NH(CH2)4 NH2+02+H20-+ spermidine
NH2(CH2)2CHO+ 3-amino-porpionaldehyde
NH2(CH2)4NH2+H202 Putrescine
Fig. 1. The oxidation of polyamines by human polyamine oxidases.
373
374
A. Ferrante, R. J. Storer & L. J. Cleland Table 1. Polyamine oxidase activity in synovial fluids from rheumatoid arthritis patients
Fluid Serum type RA synovial fluid (n = 12)* RA serum (n = 6)* Retroplacental serum (n = 58) Pooled human serum 'Control' synovial fluid (n = 3)
Enzyme activity (mU/i) (m + s.e.m.) 490 +44 89+ 36 1,722 + 114 116 144-9 +4-0
Synovial fluid or serum from rheumatoid arthritis (RA) patients. *
stopped by the addition of 50 pl trichloroacetic acid (50% w/v), precipitated protein was sedimented by centrifugation. Reaction products and substrate were separated by step-wise elution with hydrochloric acid 1-9 M (10 ml) and 4-0 M (10 ml) on Dowex 50W-X2, 200-400 mesh (BioRad laboratories, Richmond, CA) cation exchange resin (0-8 x 4 cm). Aliquots (200 pl) of the reaction mixture supernatant were applied to the columns followed by 200 p1 deionized water. The eluates were collected into polypropylene tubes, aliquots of each fraction were transferred to scintillation vials amd mixed with scintillation cocktail (Beckman Ready-solv EP). For each sample d/min was determined by counting in a Mark III liquid scintillation counter (Searle Analytic, Des Plains, TO) and percent substrate conversion calculated. Controls and blanks were included in each assay. The separation of substrate and reaction products by this method was confirmed using 3H-spermidine and '4C-spermine with dual-channel scintillation counting. Enzyme activity is expressed as international units (i.e. pmol product formed/min).
Retroplacental fluid Retroplacental fluid was collected from placentae after elective caesarean delivery at 38-40 weeks gestation as described by Klopper & Hughes (1978). Serous blood stained fluid was obtained from the maternal surface of the placenta. This fluid, which is mainly intervillous blood plus decidual and placental interstitial fluid, was allowed to clot for 30 min at 370C. The blood mixture was then centrifuged and the serum (termed retroplacental serum) was collected.
Synovialfluid Samples were obtained under local anaesthesia (xylocaine i.o.) from patients with definite or classical rheumatoid arthritis by ARA criteria classification (Mitchell & Fries, 1982) attending the Rheumatology Unit at the Royal Adelaide Hospital. Control synovial fluids were obtained at autopsy. RESULTS all 12 rheumatoid arthritis synovial that showed The results fluid samples examined were positive for PAO activity, ranging from 200 to 800 mU/l (Table 1). Only low activity was detected in 'control' synovial fluids, similar to levels found in normal serum and the serum from rheumatoid arthritis patients. However, the levels of activity in synovial fluids of rheumatoid arthritis patients were low compared to those of retroplacental serum (Table 1).
DISCUSSION These findings represent the first evidence that PAO are present in inflammatory exudates and it is possible that this enzyme(s) is part of the inflammation molecular complex which may be involved in tissue degradation and tissue regeneration in diseases such as rheumatoid arthritis. Polyamines are present in all tissues and their concentrations in tissue fluids significantly rise as a consequence of tissue damage and regeneration (Gaugas, 1980). The oxidation of these polyamines by PAO could contribute to the events occurring in various inflammatory sites. Their effects could range from stimulation and regulation of tissue cell growth to suppression of the leucocytic inflammation. PAO may be released from inflammatory macrophages and/or pannus tissue associated with affected joints of rheumatoid arthritis patients. The regulation of inflammation by PAO in disease such as rheumatoid arthritis is supported by the findings of Flescher et al. (1989), who obtained evidence suggesting that the polyamine-polyamine oxidase system is somehow involved in the down-regulation of immune reactivity associated with rheumatoid arthritis, in particular to a downregulation of interleukin-2 production. The levels of PAO levels of 500 mU/l found in rheumatoid arthritis synovial fluid would appear to be sufficient to inhibit lymphocyte proliferation, since Morgan & Illei (1980a) showed that inhibition of lymphocyte proliferation occurred as PAO activity exceeded 200 mU/l. The capacity of oxidized polyamines to inhibit the migration and oxygen radical production of neutrophils (Ferrante, 1985; Ferrante et al., 1986b) as well as cytokine production (Flescher et al., 1989) could explain the anti-inflammatory activity found in arthritic rat plasma (Persellin, 1972; Lewis, Capstick & Bers, 1976) and human rheumatoid synovial fluid (Capstick et al., 1975). REFERENCES ALLEN, J.C., SMITH, J.., HUSSAIN, J.M., THOMAS, J.M. & GAUGAS, J.M. (1979) Inhibition of lymphocyte proliferation by polyamines requiresruminant -plasma polyamine oxidase Eur. J. Biochem. 102, 153. BACHRACH, U., ABZUG, S. & BEKIERKURST, A. (1967) Cyctotoxic effect of oxidized spermine on Ehrlich ascites cells. Biochim. biophys. Acta, 134, 174. BYRD, W.J., JACOBS, D.M. & AMos, M.S. (1977) Synthetic polyamines added to cultures containing bovine sera reversibly inhibit in vitro parameters of immunity. Nature, 267, 621. CAPSTICK, R.B., LEWIS, D.A. & COSH, J.A. (1975) Naturally occurring factors in the synovial fluids of patients with rheumatic disease and their possible mode of action. Ann. rheum. Dis. 34, 213. EGAN, J.E., HAYNES, J.D., BROWN, N.D. & EISMANN, C.S. (1986) Polyamine oxidase in human retroplacental serum inhibits the growth of Plasmodium falciparum. Am. J. trop. Med. Hyg. 35, 890. FERRANTE, A. (1985) Inhibition of human neutrophil locomotion by the polyamine oxidase-polyamine system. Immunology, 54, 785. FERRANTE, A., ALLISON, A.C. & HIRUMI, H. (1982) Polyamine oxidasemediated killing of African trypanosomes. Parasite Immunol. 4, 349. FERRANTE, A., RZEPCZYK, C.M. & ALLISON, A.C. (1983) Polyamine oxidase mediated intraerythrocytic death of Plasmodiumfalciparum. Trans. R. Soc. trop. Med. Hyg. 77, 789. FERRANTE, A., RZEPCZYK, C.M. & SAUL, A.J. (1984) Polyamine oxidase-mediated trypanosome killing: the role of hydrogen peroxide and aldehydes. J. Immunol. 133, 2157. FERRANTE, A., LJUNGSTROM, I., RZEPCZYK, C.M. & MORGAN, D.M.L. (1986a) Differences in sensitivity of Schistosoma mansoni schistoso-
Polyamine oxidases in rheumatoid arthritis mula, Dirofilaria immitis microfilariae, and Nematospiroides dubius third-stage larvae to damage by the polyamine oxidase-polyamine system. Infect. Immun. 53, 606. FERRANTE, A., MAXWELL, G.M., RENCIS, V.0., ALLISON, A.C. & MORGAN D.M.L. (1986b) Inhibition of the respiratory burst of human neutrophils by the polyamine oxidase-polyamine system. Int. J. Immunopharmacol. 8, 411. FLESCHER, E.F., BOWLIN, T.L., BALLESTER, A., HOUK, R. & TALAL, N. (1989) Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis J. clin. Invest. 83, 1356. GAUGAS, J.M. (1980) Biogenic diamines and the polyamines in support and in inhibition of lymphocyte proliferation. In Polyamines in Biomedical Research (ed. by J. M. Gaugas) p. 343. John Wiley & Sons, Chichester. GAUGAS, J.M. & CURZEN, P. (1978) Polyamines interaction with pregnancy serum in suppression of lyphocyte transformation. Lancet, i, 18. HUSSAIN, J.I., SMITH, C.J. & ALLEN, J.C. (1983) Polyamine mediated inhibition of in vitro cell proliferation is not due to acrolein. Cell Tissue Kinet. 16, 583. KLOPPER, A. & HUGHES, G. (1978) Placental secretion of oestrogens and protein hormones. Arch. Gynaecol. 225, 171. LEWIS, D.A., CAPSTICK, R.B. & BEST, R. (1976) The control of rheumatic disease by endogenous protein. Biochem. Pharmacol. 25, 1435. MITCHELL, D.M. & FRIES, J.F. (1982) An analysis of the American rheumatism association criteria for rheumatoid arthritis. Arthritis Rheum. 25, 481. MORGAN, D.M.L. (1985a) Polyamine oxidases. Biochem. Soc. Trans. 13, 222. MORGAN, D.M.L. (1985b) Human pregnancy-associated polyamine oxidase:partial purification and properties. Biochem. Soc. Trans. 13, 351. MORGAN, D.M.L. (1989) Polyamine oxidases and oxidised polyamines.
375
In The Physiology of Polyamines Vol. 1. (ed. by U. Bachrach & Y. Heimer) p. 203, CRC press, Oxford. MORGAN, D.M.L. & ILLEI, G. (1980a) Polyamine-polyamine oxidase interaction: part of maternal protective mechanism against fetal rejection. Br. Med. J. 280,1295. MORGAN, D.M.L. & ILLEI, G. (1980b) Radiochemical estimation of serum polyamine oxidase activity in human pregnancy. Med. Lab. Sci. 38,49. MORGAN, D.M.L., CHRISTENSEN, J.R. & ALLISON, A.C. (1981) Polyamine oxidase and the killing of intracellular parasites. Biochem. Soc. Trans. 9, 563. MORGAN, D.M.L., FERLUGA, J. & ALLISON, A.C. (1980) Polyamine oxidase and macrophage function. In Polyamines in Biomedical Research (ed. by J. M. Gaugas) p. 303, John Wiley, Chichester. MORGAN, D.M.L., ILLEI, G. & ROYSTON, J.P. (1983) Serum polyamine oxidase activity in normal pregnancy. Br. J. Obstet. Gynaecol. 90,1194. MORGAN D.M.L., BACHRACH, U., ASSARAF, Y.G., HARARI, E. & GOLENSER, J. (1986) The effect of purified aminoaldehydes produced by polyamine oxidation on the development in vitro of Plasmodium falciparum in normal and glucose-6-phosphate-dehydrogenase-deficient erythrocytes. Biochem. J. 236, 97. PERSELLIN, R.A. (1972) Lysosome stabilization by adjuvant arthritis serum. Arthritis Rheum. 15, 44. RZEPCZYK, C.M., SAUL, A.J. & FERRANTE, A. (1984) Polyamine oxidase-mediated intraerythrocytic killing of Plasmodiumfalciparum: Evidence for the role of reactive oxygen metabolites. Infect. Immun. 43, 238. STORER, R.J., FERRANTE, A., BATES, D.J., ZOLA, H. & MORGAN D.M.L. (1988) Retroplacental polyamine oxidase: antimicrobial, antiinflamatory, antitumour and immunosuppressive properties further Characterization. In Placental and Endometrial Proteins: Basic and Clinical Aspects (ed. by Y. Tomoda, S. Mizutani, 0. Narita & A. Klopper), p. 349. VSP Science Press, Utrecht.
