The Nature of Serum Antitrypsin

Abstract

T h e e f f o r t s t h a t h a v e b e e n m a d e to d e t e r m i n e the n a t u r e o f the f e r m e n t -i n h i b i t i n g s u b s t a n c e s o f t h e b l o o d give n o definite i n f o r m at i o n c o n c e r n i n g t h e i r significance o r t h e i r c h a r a c t e r .A t one t i m e it w a s t h o u g h t t h a t the a n t i t r y p t i c Brieger and Trebing (z) stated that 9o per cent. of the patients suffering from carcinoma or sarcoma, whom they had examined, showed a n increase of antitrypsin in the blood. Von Bergmann and Meyer (2) confirmed this observation, though they also fl?und a similar increase in 24 per cent. of non-cancerous patients. Recent work indicates that the increased ferment-inhibiting action of the serum cannot he relied upon as a diagnostic test for cancer. It is frequently present in the acute infections, such as pneumonia, typhoid fever, etc. ; in chronic infections, such as tuberculosis and syphilis; in Graves' disease; and in severe anemias. The action of the serum has been ascribed, to chemical constituents and to specific immune bodies which act as antiferments. Meyer (3) believes that the antiferment is a true antibody, and that the ferments of the tissue cells act as antigens. He concludes that trypsin and leucoprotease are not so important in this respect. Eisner (4) and Wiens (5) also believe that the antiferment is a true antibody, ~out that the antigen is the ferment liberated by the polymorphonuclear cells. On the other hand, Jfirgensen (6) found no relation between the antitryptic index and leucocytosis. Halpern (7) inoculated dogs with the, pancreas of dogs, and found an increase in antitrypsin, but no increase in antipepsin. Eisner (4) studied the inhibiting action of serum against various ferments, and concluded that it possessed a special att~nity for trypsin. Some writers have asserted that the serum is more active against trypsin of the same species, but Weil (8) and others have disgroved this.Morgenroth (9) thought that he obtained a specific antirenin by inoculating animals with renin, while Achalme (io) states that he produced a specific antitrypsin by inoculating animals with trypsin. Other investigators repeated the work of Morgenroth and Achalme and have failed to confirm their results. Hamburger (II) showed that sodium chloride destroys pepsin in a neutral solution, thereby invalidating the evidence that a sl~ecifie antipepsin is present in the blood; immune bodies are active only in a neutral or slightly alkaline reac-

The Nature of Serum Antitrypsin and its Relation to Autolysis and the Formation of Toxins in Infection and in Anaphylaxis.

“…Various investigators have been struck by the uniformity of the main manifestations of bacterial toxacmia in animals of the same species and have come to the conclusion that the symptoms are due not to specific bacterial endotoxins but to a non-specific poison formed (1) either from the bacteria themselves by the action on them of antibodies and complement (Teale and Embleton [1], Vaughan [2]); or (2) from the plasma of the infected animal (Jobling and Petersen [3]). These last authors believe that bacteria can adsorb antitrypsin and so allow the plasma proteolytic enzymes to give rise to proteose-like toxic bodies from the animal's own body fluids.…”

The Mechanism of Anaphylactic Shock

“…In a previous paper we have shown that there is no element of specificity in so far as the proteases are concerned in the digestion occurring in the Abderhalden reaction (I3). The digest is obtained from the serum proteins and is brought about by changes in the colloidal state of dispersion of the serum induced by the antigen introduced as a substrate, resulting in what may be termed local areas of antiferment deficiency, due either to an actual adsorption of antiferment by a formed substance, such as a precipitate, or to a change in the degree of dispersion of the unsaturated lipoids upon which the antiferment property depends, as we have previously demonstrated (14). If a protease is present in such sera a positive reaction can occur; if not, the digestion does not take place.…”

Studies on the Inhibition of Proteolytic Enzymes by Serum

“…Serum proteolytic inhibition was found to be increased in association with many diseases. Jobling and Petersen presented a comprehensive review of the subject in 1914 (2), and Grob reviewed the interval literature in 1942 (3). The physiological significance of proteolytic inhibition and the reasons for its increase with disease are not yet known.…”