Parenteral Retention of Undenatured Foreign Proteins.

Abstract

Ice-chest ripened anti-horse rabbit precipitin contains: (a) a high-titer, highly active specific precipitin for horse proteins, and (b) a low-titer, relatively inert “non-specific precipitin” for canine proteins. Acting together these two precipitins presumably function as (c) a precipitin for hypothetical proteins of intermediary, “hybrid,” or horse-canine specificity.

By the use of such antisera we have obtained precipitin graphs which suggest a 200% to 400% increase in hypothetical “hybrid” proteins in the canine circulation by the end of 18 days, with a 25% retention of these hypothetical intermediary products at the end of 3 months. 1 That the intermediary substances thus demonstrated are partially caninized horse proteins or their equivalent and not mere toxic increases in some normal non-specific canine factor is shown by our failure to obtain similar increases and retentions on intravenous injection of heterologous proteins (e. g., beef serum).

Parallel with these tests we are following the parenteral history of the undenaturized residue of the injected horse proteins by means of antisera from which the canine and “hybrid” factors have been “absorbed”. To prepare this altered precipitin 2 cc. crude antiserum is diluted with 7 cc. Ringer's solution, and 1 cc. normal canine serum then added. The mixture is incubated 2 hours, stored in the icechest over night, then passed through a Berkefeld filter. The “reduced precipitin” thus obtained gives no demonstrable reaction with normal canine proteins and presumably no reactions with proteins of dominant canine characteristics.

Our results to date indicate that undenatured horse proteins decrease rapidly in the canine circulation. But 12.5% to 25% of the routine initial dose is demonstrable at the end of 1.5 days, and but 1 % to 3% by the 25th day. From 0.01% to 0.1% is present at the end of three months.