Contribution of the Kallikrein/Kinin System to the Mediation of ConA-Induced Inflammatory Ascites

Intraperitoneal administration of concanavalin A (ConA, 25 mg/kg b.w.), a cell-binding plant lectin was used for inducing inflammatory ascites, and potential inhibitors were tested in 1 h and 2.5 h experiments, i.e. still before the major influx of leucocytes. At the end of the experiment the peritoneal fluid was collected and measured

Fehérje-szénhidrát kölcsönhatások vizsgálata in vivo kísérletekben = Study of protein-carbohydrate interactions with in vivo experiments

Elsősorban a növényi lektinek biol. hatásait vizsgáltuk, mégpedig a hemaggl. elkerülésére i.p. fecskendezve rágcsálókba. A mesothel sejtfelszíni glikoprotein oldalláncain megtapadó, különböző spec. lektinek (és polikationok is) fehérje-dús ascites-folyadék szekrécióját váltották ki, nem-kovalens keresztkötések képzése miatt. Egyes lektinek i.p. beadása után néhány óra késéssel a pleura és a pericardium is szekretálni kezdett, a szövet-spec. hatás okát tisztáztuk. Ezután ConA-t használtunk modell-lektinként. Ellentétben az orális hatással, a peritoneális hatás nem idegi mediációjú. Eleinte a pro-inflammatorikus mediátorok sem vesznek részt benne, csak néhány óra elteltével. A kallikrein-gátló aprotinin részben gátolt, de az eNOS gátlása nem hatott. Az ér permeabilitást növelő hisztamin és lipopoliszaccharid (LPS) dózis-függő ascites-gátlást mutatott, amit csak direkt a mesothel sejtekre irányuló hatással lehet magyarázni. Tehát fordított hatásuk van a mesothelre, mint az endothelre. Ez a munka legfőbb eredménye. -- Szubakut kísérletekben a hashártyára tapadt leukocyta aggregátumok lokálisan leukocyták kilépését váltották ki az erekből, ami a WGA esetén szelektív neutrophil diapedezis volt. Sok jelét találtuk a lektinek fokozatos felszívódásának a hasüregből. -- Módszert dolgoztunk ki a ConA-LPS reakció agaróz-gélben való vizsgálatára és összehasonlítottuk a különböző szerkezetű LPS-ek reakcióit. -- Orális LPS utáni bél morfometria negatív volt. | Primarily the biol. effects of plant lectins were studied, injected i.p. to rodents to evade haemagglutination. Lectins with different specificities (and also polykations) that attached to the glycoprotein side-chains on the surface of mesothelial cells induced secretion of protein-rich ascitic fluid, due to the formation of non-covalent cross-links. With a delay of several hours after the i.p. inj. of definite lectins the pleura and pericardium also began to secrete; the cause of this tissue-specific effect was clarified. Later ConA was used as a model lectin. Contrary to the oral effect, the peritoneal one was not neurally mediated. At first the pro-inflammatory mediators were not involved, only after a couple of hours. Aprotinin, a kallikrein inhibitor, exerted partial inhibition, but the inhibition of eNOS was without effect. Histamine and LPS, agents increasing vascular permeability, inhibited ascites, which can be explained only with a direct effect on mesothelial cells and with opposite effects on mesothel and endothel. -- In subacute experiments leukocyte aggregates attached on the peritoneum induced the vasc. diapedesis of leukocytes, which was a selective neutrophil diapedesis, when WGA was applied. Gradual absorption of the lectins from the peritoneal cavity was indicated. -- A method was developed for the study of ConA-LPS reaction in agarose gel and the reactions of diff. LPS species were compared. Oral LPS did not alter intestinal morphometric traits

Modulation of ConA-induced inflammatory ascites by histamine — Short communication

The early phase of the ConA-induced inflammatory ascites was studied, with special reference to histamine. Concanavalin A (ConA), a cell-surface binding lectin was injected i.p. (25 mg/kg bw) to mice. After 1 h the animals were killed, the ascitic fluid collected and measured. Other agents were injected s.c., 10 min before the ConA-challenge. Exogenous histamine markedly inhibited the ConA-induced ascites. Release of endogenous vasoactive agents from the mast cells by Compound 48/80 had a similar, but slight effect. Cromolyn, a mast cell stabilizing agent, and chloropyramine, a histamine H1 receptor antagonist was ineffective. Although histamine increases endothelial permeability, it did not enhance the formation of ascitic fluid, on the contrary, it inhibited the ConA-induced ascites, presumably due to its known hypotonic effect. It is concluded that ConA-induced ascites is not mediated by mast cell histamine

Mediation of inflammatory ascites formation induced by macromolecules in mice

The first 60-min phase of inflammatory ascites formation was studied by intraperitoneally (i.p.) administered macromolecular inducers: yeast cell wall zymosan binds to specific macrophage receptors, polyethyleneimine (PEI) and concanavalin A (ConA), produces non-covalent cross-links on the surface of various cells, while λ-carrageenan may function as a contact activator. Depletion of peritoneal macrophages was performed by overnight pretreatment with diphtheria toxin in transgenic mice, resulting in a significant (p < 0.01) decrease in the induced formation of ascitic fluid. It was shown that induced ascites is mediated partly (PEI, ConA, and carrageenan) or completely (zymosan) by peritoneal macrophages. Inhibition of prostanoid synthesis with indomethacine or of the kallikrein/bradykinin system with aprotinin also produced a significant (p < 0.01) but incomplete inhibition. A slight additivity occurred between the different inhibitory effects. In another series of experiments, the i.p. administration of bradykinin (without a macromolecular inducer) also produced marked ascites, which was not affected by macrophage depletion. The origin of the macrophage-independent part of the induced ascites is best explained by the deformation of the mesothelial cell surface, resulting in signal transfer to the underlying endothelium and the passage of ascitic fluid in the opposite direction. The soluble mediators are represented by prostanoids, bradykinin and other, unidentified agonists

Intraclonal variation in defence substances and palatability: a study on Carex and lemmings

Clonal sedges consist of integrated ramets at different development stages. Many of these sedges are important food for herbivores, yet differences in herbivore preferences and defence allocation between ramet development stages have not previously been evaluated. In this study we investigated intraclonal ramet variation in level of plant defence and nutrient compounds and intraclonal ramet preferences by lemmings (Lemmus trimucronatus) in field samples of a rhizomatous sedge (Carex stans). Plant defence was measured as the level of proteinase inhibitor activity (PIA) and the ratio of PIA to soluble plant proteins (SPP), whereas plant nutrients were measured as the level of soluble plant sugars (SPS) and SPP. Flowering ramets generally had a higher content of defence compared to vegetative ramets, which is consistent with the optimal defence theory predicting that defence compounds are allocated to the ramet stage of the highest fitness value. Compared to vegetative ramets, the flowering ramets had a lower content of SPP and a higher content of SPS. The lemmings showed preference differences between the ramet development stages, and to a large extent the ramet content of defence compounds and nutrient compounds covaried with these preferences in the predicted way. This study shows that defence allocation between ramet development stages of the clonal sedge Carex conforms to predictions of the optimal defence theory