Hæmmaglutination by horse serum and jaundice in mice / C.C. Okell and G.I. Steed.

  • Okell, C. C. (Charles Cyril), 1888-1939.
Date:
[1926?]
Catalogue details

Licence: In copyright

Credit: Hæmmaglutination by horse serum and jaundice in mice / C.C. Okell and G.I. Steed. Source: Wellcome Collection.

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    P.3 746' Reprinted from The Journal OF PATHOLOGY AND BACTERIOLOGY, Vol. XXIX., 1926, pp. 132, 133. HEMAGGLUTINATION BY HORSE SERUM AND JAUNDICE IN MICE. C. C. Okell and G. I. Steed. Wellcome Physiological Research Laboratories, Beckenham, Kent. While testing about 500 specimens of therapeutic horse sera for their toxicity to mice, it was found that one serum injected intravenously constantly gave rise to jaundice which in the majority of cases was fatal within twenty-four hours in a dose of 0’5 c.c. The horse from which this sample had been obtained had at no time had an injection of mouse cells or tissue of any kind. On further investigation this jaundice was found to depend upon the marked agglutinative power of the serum in question on the red cells of mice. The serum had practically no haemolytic power in vitro for mouse cells when either guinea-pig or mouse serum was used as complement: faint trace of haemolysis was noted when mouse complement was employed and this only when the highest relative amounts of serum to cells were used. The haemagglutinative power of the serum was however high, at least twice as high as that of the majority of samples of horse sera. Serum of moderate agglutinative power can be concentrated by the usual ammonium sulphate method so that it gives rise to jaundice. A search was made and a sample of serum from another horse was found which agglutinated mouse cells in vitro to a high titre. It could be correctly predicted that, like'the original serum, this would cause jaundice in mice. Mouse cells which had been previously agglutinated in vitro, washed three times, shaken and injected into mice produced jaundice but usually no immediate embolic effects. On the other hand injection of even large amounts of mouse haemoglobin did not produce jaundice. The phenomenon we were observing was clearly a haemolytic jaundice due to the effect of agglutinin on mouse cells and though produced by a converse method seemed to be essentially the same as that occurring after transfusion of human patients with the blood of unsuitable donors. So far we have not been able to find records of haemolytic jaundice produced experimentally as a pure haemagglutinative effect (but see R. Bieling and S. Isaac Zeit. ges. exp. Med. 1921, xxv., 1; 1922, xxvi., 251; xxviii., 154). There appears to be no damage to any other tissue and no immediate intravascular lysis of red cells. Conditions should therefore be favourable for studying the mechanism of haemolytic jaundice and particularly the phagocytic activities of the reticulo¬ endothelial system on red cells which are damaged but are still capable of circulating. The amount of serum injected when mixed with the circulating cells of the mouse constitutes potentially a very powerful agglutinative system. A few minutes after the serum has been injected one may remove a sample of blood from the mouse into saline, Ringer’s solution, citrate-saline or isotonic glucose and massive agglutination of the red cells takes place. When withdrawn the blood shows no immediate signs of agglutination to the naked eye and if withdrawn into mouse plasma it takes several minutes to show obvious agglu¬ tination. For a time we thought that no agglutination proper was taking place in the vessels of the mouse and that it was only after withdrawal and inter¬ ference with the normal balance of the blood that it occurred. But careful observation of the circulation of the blood in the mesenteric capillaries and veins after injection of the agglutinating serum convinced us that agglutination occurs but that the inhibitory effect of the whole blood, aided no doubt by the com¬ motion of the circulation, prevented agglutination from giving rise to immediate ns