The preservation of membranes by biologically-active agents

Biological membranes are under constant threat of rupture by noxious substances present in the same, or neighbouring, cells. These materials (normally restrained by another membrane) can become liberated as the result of a pathological process, such as an infection, allergy, or auto-immune phenomenon. Of these substances, histamine produces a violent but short-lived reaction, but there are long-acting analogues. 

Before discussing what is being done to protect vital membranes, it is useful to note some details of the mechanism by which one cell can damage another. Chief of the offenders are the mast cell and its circulating analogue the basophil leucocyte. Each mast cell has up to 5 million receptors for the antibody known as IgE. The mere binding of IgE to the cell does not trigger a release of 

The bronchospasm of human asthma is caused by much longer-acting substances than histamine. Formerly one spoke of SRS (slow-reacting substance), but the injury is now known to arise from a family of four leukotrienes, prostaglandin-related substances liberated from the human lung. Most typical is leukotrieneD 14.21) (Morris a/., 1980). 

A potent and selective inhibitor of biosynthesis of the leukotrienes is the 5,6-methano derivative of leukotriene-A4 ( methano implies a three-membered carbocyclic ring formed by the bivalent substituent CH.j) (Nicolaou, Petasis and Seitz, 1981). Another approach is afforded by the pyrazoline drug 14.22) known as BW 755C which went into clinical trial in 1980. It inhibits an enzyme which synthesizes the leukotrienes (Higgs, Flower and Vane, 1979). 

The action of cromolyn sodium is highly specialized, for it does not protect the mast cells of skin. It is not absorbed when taken by mouth. It has been used with some success in preventing hay fever and as a prophylactic (given orally) against food allergens in the gut. 

Considerable developments in treating inflammatory diseases by the prophylactic conservation of membranes seem certain to play a much greater part in medical treatment than formerly. 

For further reading on the physics and chemistry of interfacial phenomena, see Matijevic and Eirich, (1969). 

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The injury of membranes by biologically active agents. 603 The preservation of membranes by biologically active agents. 608... 

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