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PubMed1984

[The concept of mediators in acute inflammatory reactions].

The evolution of ideas about inflammation oscillates between two poles: sometimes the cell aspects of inflammation are described, with leucocyte adhesion to the vessel wall followed by migration into the tissues and phagocytosis - at other times it is the turn of the chemical intermediaries accounting for the damage to blood vessels, in which case vasodilatation, permeability and chemotaxis are given particular emphasis. The present tendency is to concentrate on the origin of these intermediaries and their relationship to the different cell populations found in situ. Before defining the relationship between cells and acute inflammatory mediators, an inventory needs to be drawn up of the latter. They can be divided into three main categories, according to the manner of their involvement at the site of inflammation: preformed agents, which are then released; mediators formed as a result of enzyme influences, cell-derived or not, from inactive precursors; the enzymes themselves which attack the structures involved in the lesion. These various mediators are thus traceable to specific mechanisms of formation or release, from cell populations that are now clearly identified. From an understanding of how the inflammatory focus has been colonised by the different leucocyte populations and a knowledge of their enzymatic potential, conclusions can be drawn not only about the mediators concerned but more especially about the pharmacological agents that must be mobilised in order to neutralise their clinically apparent effects.

Acute Disease↗
PubMed1984

Effect of second tumors and of prostaglandin-leukotriene inhibitors on radiation therapy of transplanted rodent tumors.

The prostaglandin and leukotriene inhibitor sodium meclofenamate (SM) failed to influence radiation therapy induced regression of 6C3HED Gardner lymphosarcoma in C3H mice. Recurrence after radiation therapy, however, was reduced by treatment with SM. During these experiments, we observed that if a tumor was "cured" by radiation therapy, it required inoculation of a larger number of cells to establish a second tumor. Presumably, a certain degree of immunity has developed. On the other hand, if a second tumor was already established, less tumor cells were needed to establish a third tumor. This may be related to immuno-suppressor products of the second tumor. This effect could be partly inhibited by SM, suggesting that prostaglandins and leukotrienes may be involved in this phenomenon.

Animals↗
PubMed1984

Release of slow reacting substance from rabbit ocular tissues.

Investigations were carried out to determine whether any slow reacting substance (SRS) is released from the ocular tissues. The SRS activity was bioassayed using the guinea pig ileum in the presence of mepyramine and atropine. An SRS-specific antagonist, FPL55712, was also used to confirm SRS-induced ileum contraction. Incubation of the ocular tissue fragments of the rabbit with a Ca-ionophore A23187 resulted in a marked release of the SRS in the potency order of the choroid, ciliary body, conjunctiva and iris. The rabbit was sensitized with bovine serum albumin and complete Freund's adjuvant. Experimental uveitis was induced by injection of antigen into the vitreous body the sensitized rabbits. The SRS could not be detected in the aqueous humor 10-24 hours after the antigen injection but it was released markedly into the vitreous. The SRS from the vitreous humor of the rabbits with experimental uveitis was purified by high performance liquid chromatography, and leukotriene C4 and leukotriene D4 were identified. It was suggested that release of the SRS from the ocular tissues plays a role in allergic and nonallergic uveitis.

Animals↗
PubMed1981

Action of substance P and an analogue on blood pressure and avoidance learning in rats with spontaneous hypertension (SHR).

Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").

Animals↗
PubMed1981

The mast cell.

The mast cell is the cellular basis for immediate hypersensitivity reactions. The specificity of the immediate hypersensitivity reaction is attributable to IgE molecules fixed to specific membrane receptors which, when stimulated by specific antigen, initiates the process of degranulation of the mast cell. The granules provide three separate sources of biologic activity: performed or primary mediators, newly generated or secondary mediators, and activities associated with the granular matrix. A number of biologic consequences are generated in response to these mediators and these include: increased vascular permeability, vasodilation, smooth muscle spasm, polymorphonuclear leukocyte chemotaxis, stimulation of adenylate and guanylate cyclase, superoxide radical generation, prostaglandin formation, mucous and gastric acid secretion, hypotension, tissue destruction, and mononuclear leukocyte infiltration. This pharmacopia of activities accounts for the clinical aspects of allergic diseases, suggests that the mast cell granule may be involved in the host's defense against parasitic infections, and is compatible with a suggested role of the mast cell as a widely distributed, monocellular endocrine system.

Animals↗
PubMed1983

Measuring leukotrienes of slow reacting substance of anaphylaxis: development of a specific radioimmunoassay.

Rabbits were immunized with leukotriene C4 (LTC4) coupled to thiolated keyhole limpet hemocyanin (KLH) by using 6-N-maleimidohexanoic acid as a spacer molecule. Immune serum was obtained with 7.9 nmol of LTC4-specific immunoglobulin per milliliter and a mean association constant of 2.1 X 10(9) M-1. A radioimmunoassay was developed that detected 0.1 pmol of LTC4 per 1-ml sample. LTD4 and LTE4, three isomers of LTC4, the sulfones of LTC4, LTD4, and LTE4, and one isomer of LTD4 reacted to varying degrees in the assay. A number of other structurally related compounds, such as LTB4 and 5-HETE, did not react. Conditions were established to determine LTC4 levels in human plasma without loss of LTC4 during sample preparation and without the need for extraction procedures before the measurement of LTC4.

Animals↗
PubMedDate not supplied

Bronchospasm mechanisms in experimental microbial sensitization. II. Pathochemical stage.

The pathochemical mechanisms of bronchospasm have been studied using various type of experimental allergies to microbial antigens. It was established that in guinea pigs with type I allergies isolated lung bronchospasm was mediated by histamine and SRS-A. Bronchial response to immune complexes type III were produced by the activation of complement with subsequent degranulation of mast cells and histamine release. Type IV hypersensitivity (lymphokine-mediated bronchospasm) was manifested without histamine, acetylcholine and mast cell involvement. The response to lymphokine was blocked by atropine. The spasmogenic y lymphokines are large molecular thermolabile substances.

Allergens↗