Search

Production of a factor activating leucocyte procollagenase by tissue culture of rheumatoid synovium was shown. The activator was isolated, partly purified, and shown to be thermolabile, nondialysable, and had no activity toward casein, haemoglobin, histones, and PZ-peptide. The activity of the activator was partly decreased by trypsin. [ABSTRACT FROM PUBLISHER]

The products resulting from proteolytic degradation of human fibrinogen (FDP) were found to induce the release of histamine from rat peritoneal mast cells. Low molecular weight, dialysable peptides (FDP) showed the highest dose dependent, histamine releasing activity. Histamine release induced by FDP was effectively inhibited by the gold compound auranofin at a concentration of 10(-5)-10(-7) mol/l and also by the non-steroidal anti-inflammatory drugs BW 755c, timegadine, medosan, naproxen, and aspirin at the higher concentration range of 10(-4)-10(-6) mol/l. It is concluded that the release of histamine from mast cells may be modulated to some extent by anti-inflammatory drugs, especially auranofin, BW 755c and timegadine, a functional property which may be beneficial in the management of joint disease. [ABSTRACT FROM PUBLISHER]

The article presents information on research related to histamine receptors in synovial cells of patients affected with osteoarthritis (OA). OA causes development of bony spurt and cysts. Histamine effects the joints and mast cells in the synovial are major source of them. The study confirmed the presence of histamine in the synovial cells and their expression in OA joints.

Object: To examine the distribution of mast cells in human placental tissue and to analyse the interactions between mast cell mediators (histamine and serotonin (5-HT)) and contractile activity of the uterus during delivery., Design: 34 placentas were examined. Histamine and serotonin levels in placental samples were estimated using fluorymetric method. Distribution of mast cells were analysed immunohistochemically on the same material., Setting: Dept. of Pathophysiology, Medical Academy, Warsaw, Poland. (*) Laboratory of Developmental Neuropathology Centre of Experimental and Clinical Medicine, Polish Academy of Sciences, Warsaw. (**) Clinic of Obstetrics and Gynecology, Second Medical Faculty, Medical Academy, Warsaw., Subjects: 34 women, whose pregnancies ended in time and in preterm delivery, with normal, abnormal or without contractile activity of the uterus (elective cesarean section)., Main Outcome Measurements: Comparative charts of histamine levels in placental samples in relation to term and course of the labour., Results: Concentration of histamine in placental cuts obtained from maternal surface of the placenta was significantly higher in the case of delivery without contractile activity of the uterus (elective cesarean section). Immunohistochemical identification of mast cells proved, that in regions located close to fetal surface of the placenta and in connective tissue foci, mast cells were most numerous., Conclusions: It is postulated that the simultaneous release of mast cell mediators (especially histamine) in placental tissue could be an important factor for evoking contractile activity of the human uterus, initiating labour. Further investigations should give answers on the points of these dependences.

During ischaemia, there was no apparent change in malondialdehyde (MDA) content in rat myocardium. However, reoxygenation resulted in a significant increase in MDA content. The changes evoked by ischaemia and reoxygenation were significantly attenuated by addition of fenistil (histamine H1 receptor antagonist). Enzymatic antioxidant systems were not significantly modified in the different periods of ischaemia and after 30 min of reoxygenation. It is suggested, that maintenance of an adequate endogenous antioxidant reserve during ischaemia may be important in recovery upon reoxygenation.

The ability of various peptides cleaved by plasmin from human fibrinogen and fibronectin or fibrinogen- and fibronectin- related synthetic peptides to induce histamine release from mast cells and collagenase and elastase from PMN-leukocytes was examined. Low molecular weight fibrinogen degradation products showed dose dependent secretion of collagenase. These peptides (mol. wt. 1.4 kD) at the concentration of 10(-5) M released about 47% of collagenase and 13% of elastase. Synthetic fibrinopeptides A and B had a similar strong collagenase releasing potency and also released histamine from mast cells. Peptides from plasmin digestion of fibronectin containing cell attachment site with sequence Arg-Gly-Asp-Ser and also synthetic peptide reproducing this amino-acid sequence at the concentration of 1000 micrograms/ml released about 50% of collagenase and 55% of elastase from PMN-leukocytes. Moreover peptides containing cell attachment and gelatin binding site induced histamine release from mast cells. The association of fibrinogen and fibronectin degradation with activation of mast cells may motivate the treatment with antihistaminic drugs of all pathological conditions where the intensive protein degradation takes place.

We have examined the effects of auranofin and some nonsteroidal anti-inflammatory drugs (NSAID) on the release of gelatinase from rat neutrophils. Two preparations of neutrophils were used, one derived from normal blood and the other from the inflamed pleural fluids of carrageenin-elicited pleurisy. Both neutrophil preparations released gelatinase in response to stimulation by serum-treated zymosan (STZ) or concanavalin A (Con A). Control, blood-derived neutrophils exposed to STZ produced more than a four-fold increase in the release of gelatinase, a response significantly inhibited by the presence of auranofin at 10(-5) and 10(-4) M. Inflamed, pleural neutrophils exposed to STZ produced a doubling in gelatinase release and this was also inhibited by auranofin at 10(-5) and 10(-4) M. The release of gelatinase by control neutrophils (no stimulation) or by neutrophils exposed to Con A was enhanced by 10(-6) M auranofin. In contrast, the NSAIDs aspirin, piroxicam, sulindac, indomethacin and naproxen had no inhibitory action on neutrophil gelatinase release. We conclude that auranofin is an effective inhibitor of gelatinase release from neutrophils and this property may represent a contributory factor assigned to the beneficial therapeutic action of gold salts.

During the course of carrageenan-induced inflammation in rats major changes were observed in the activities of neutrophil granule enzymes. The activities of three enzymes--gelatinase, collagenase and beta-glucuronidase, the markers of three different types of granules, have been measured and compared to those of a control group of animals. Total collagenase and gelatinase activities of control rats were 59.4 +/- 3.6 (mean +/- SD) and 23.0 +/- 2.9 units/mg protein, respectively. Significantly reduced levels of both collagenase (35.6 +/- 2.5 units) (p less than 0.05) and gelatinase (7.1 +/- 0.7 units) (p less than 0.001) were measured in the blood neutrophils of inflamed rats; and the collagenase activity of neutrophils derived from inflamed pleural exudate was also significantly decreased to a level of 19.7 +/- 1.8 units/mg protein (p less than 0.01). However, the gelatinase activity of exudate neutrophils did not differ from that of blood cells of inflamed rats. In contrast, no change was found for the beta-glucuronidase activity in blood neutrophils of control and inflamed rats. These observations support the concept that during the inflammatory response in rats, neutrophils in the circulation may become activated as judged by the extracellular secretion of collagenase and gelatinase. Therefore, neutrophils accumulating in acute inflammatory lesions contain decreased levels of collagenolytic enzymes and the significance of this observation is discussed.

1 Collagen degradation products (CDP) resulting from bacterial collagenase digestion were fractionated by gel filtration and their biological activities in rats were estimated. 2 CDP induced the following kinin-like effects: increase in permeability of skin blood vessels, contraction of the isolated intestine of the rat, depression of locomotor activity and of motor coordination. 3 The most active CDP fraction was CDP III containing peptides of mol. wt. < 1000 D with a high percentage of hydroxyproline. 4 As compared with bradykinin, CDP III was less active in the skin permeability test and was 15,000 to 20,000 fold less effective in induction of isolated intestine contraction. 5 Depression of the CNS induced by 30 microgram of CDP III administered into the brain ventricle was similar to that observed after 4 microgram of bradykinin given by the same route. 6 CDP III prolonged the duration of sleep evoked by thiopentone and enhanced the threshold of convulsion induced by pentazol. 7 The activity of CDP in comparison to other low molecular weight peptides is discussed.

1. An activator catalysing specifically conversion of latent forms of human leucocyte collagenase and gelatin-specific protease into the active forms, has been isolated from rheumatoid synovial fluid and purified 55-fold with a yield of 16%. 2. Molecular weight of the activator is about 35 000. 3. The activator is thermolabile, and is irreversibly inactivated at pH below 5.5 or in the presence of low concentrations of trypsin or papain; it is resistant to the action of lysozyme, hyaluronidase, diisopropylfluorophosphate, soybean trypsin inhibitor, p-chloromercuribenzoate, iodoacetamide and dithiothreitol. 4. The activator did not show any activity towards collagen, gelatin, casein, haemoglobin, histones, elastin or p-phenylazobenzyloxycarbonyl-peptide.

The intrapleural injection of carrageenin into rats caused accumulation of leucocytes in the pleural cavity and changes in blood leucocyte populations. An increased number of polymorphonuclear (PMN) leucocytes was observed. The peripheral blood PMN leucocytes of untreated rats contained 33.2 nM reduced glutathione/10(7) cells and collagenase mainly in the latent form. During experimental pleurisy in blood leucocytes as well as in the leucocytes obtained from the pleural exudate, the level of reduced glutathione decreased significantly by about 33% (22.4 nM/10(7) cells) and parallel collagenase activation up to 80-100% was observed. Two tested antiinflammatory drugs, Timegadine and piroxicam, which significantly inhibited activation of latent collagenase during the course of inflammation and partially protected reduced glutathione against oxidation. These results suggest that the activation of latent leucocyte collagenase in vivo via the disulphide-thiol interchange reaction may be coupled to the glutathione cycle and regulated by variation in its redox potential.

Treatment of rats with histamine releaser compound 48/80 caused changes in blood leukocyte populations. An increased number of PMN-leukocytes was observed. Tritoqualine only modestly reduced the number of granulocytes. In animals treated with compound 48/80 an activation of PMN-leukocyte latent collagenase of up to 80% was observed. This activation was partially inhibited (about 40%) in animals pretreated with tritoqualine. The results presented suggest that the beneficial effect of tritoqualine in allergic diseases may be in part connected with an indirect inhibition of collagenase activity.

Experimental pleurisy in rat and intraperitoneal injection of histamine, serotonin and the histamine releaser compound 48/80 caused changes in blood leucocyte populations. An increased number of PMN-leucocytes was observed. The peripheral blood PMN-leucocytes of non-treated rats contained collagenase mainly in the latent form. During experimental pleurisy and after treatment with histamine, serotonin and compound 48/80 activation of latent collagenase of up to 90-98% was obtained. Mepyramine, cimetidine and timegadine inhibited activation of latent collagenase by compound 48/80. It is suggested that histamine is involved in the process of activation of leucocyte collagenase in the course of inflammation.

The effect of collagen degradation products by bacterial (BCDP) and synovial fluid collagenase (SCDP) on histamine release from peritoneal mast cells of rat was estimated. Some BCDP as well as SCDP released 60-80% of mast cell histamine. In BCDP fraction the most active were BCDP II (m.wt. 13 kD) and BCDP III (m.wt. 6 kD). The last contained the highest percentage of hydroxyproline. As compared with bradykinin, BCDP III was about 50 fold more active as histamine releaser.