THE THERMOSTABILE ANTICOMPLEMENTARY CONSTITUENTS OF THE BLOOD
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1906)

Blood serum contains normally certain principles which inhibit serum haemolysis by interfering with the action of complement. In the case of most sera the anticomplementary action appears only after heating to 56 degrees C. or higher. The inhibiting action of this principle is directed against alien as well as native complements, and is non-specific in character. It would appear as if the inactivation of serum at 50 degrees C. or thereabouts were due to a partial liberation of the antilytic principle which just about suffices to neutralize the action of the native complement. As the temperature of the serum is raised, up to a certain point, more and more of the antilysin is set free until the serum comes to contain an overplus, in excess of the quantity neutralizing its own complement, which is capable of interfering with the action of additional native or alien complements. Serum heated to 90 degrees C. is less antilytic than serum heated to 70 degrees C., either because the antilysin has entered into new, more stable compounds which prevent its action, or, as is more probable, because of the liberation from the serum of a second group of principles in themselves haemolytic directly, or indirectly by increasing the power of serum haemolysins (auxilysins). This latter action tends to mask and to suppress the inhibitory influences of the antilysin. The antilysin is removed from serum by digestion with many kinds of blood corpuscles which, apparently, absorb the principle. While, by reason of this treatment, the serum is deprived of its inhibitory power, the corpuscles have acquired greater resistance to serum haemolysins. By treating blood serum and corpuscles with ether the antilysin can be extracted. The ethereal extract, freed from lecithin and certain related bodies, contains the antilysin in a concentrated but not in a pure form, which can now be taken up in saline solution in which it dissolves. The saline solution of the antilysin, which for convenience has been denominated "protectin," behaves in all respects like the native antilytic sera except that it is uninfluenced by temperatures of 90 degrees C. or even higher temperatures. Protectin inhibits serum haemolysis directly by neutralizing complement and indirectly after absorption by corpuscles by increasing their resistance. Hence it is highly probable that the antilytic principle of heated serum and protectin extracted from serum and corpuscles are the same substance. Thermostability is one of the characteristic properties of protectin. Serum and corpuscles, first dried, may be heated to 150 degrees C. without losing the protecting principle, and the principle persists in such heated products for at least two years. Protectin in solution is unaffected by a temperature of 100 degrees C. maintained for one hour, and suffers only slight reduction in activity at the expiration of two hours; while temperatures ranging from 135 degrees to 150 degrees C. bring about marked reduction in protective power. As these alterations are produced by high temperatures the reaction of the solution changes from acid, through neutral, to alkaline.