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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]

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 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.

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.

Experimental pleurisy induced by carrageenin in rats caused an accumulation of PMN-leukocytes in the pleural cavity and changes in the blood leukocyte population. During the course of the inflammation involved, up to 90-98% activation of latent collagenase was observed in blood PMN-leukocytes and in leukocytes obtained from pleural exudate. The NSAIDs tested for their effect on this process had significant inhibitory effects on both exudate and leukocyte accumulation as well as on the activation of latent collagenase. Timegadine, medosan and sulindac were most effective in preventing collagenase activation, felden and naproxen were less effective, and peroxinorm was without an influence, whereas indomethacin destroyed collagenase activity. These results suggest that the protective effects of NSAIDs against the activation of latent collagenase could be one of their therapeutic actions.

Rat peritoneal mast cell extract contains an activator of latent human granulocyte gelatinase. The activator has been partially purified and characterized. It shows a similarity to rat mast cell chymase in several properties including its molecular weight, substrate specificity and sensitivity to inhibitors. The activation of latent gelatinase with rat mast cell protease is dependent on protease concentration, incubation time and is mediated through the catalytic site of the activator. The significance of mast cell protease in the regulation of collagenolytic enzymes is discussed.

The physicochemical properties of three latent collagenases derived from rheumatoid synovial fluid, polymorphonuclear leucocytes and culture medium of rheumatoid synovium were compared. It has been shown that synovial fluid enzyme is similar to that of synovium collagenase from tissue culture and differs significantly in molecular size and protein charge from granulocyte collagenase. The results indicate that the latent, trypsin-activable collagenase present in rheumatoid synovial fluid is not of granulocytic origin and seems to derive from the synovial membrane.

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.

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.

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.