Release of inhacellular enzymes into serum1

Serum lactic acid dehydrogenase (LDH) activity of normal rabbits is increased after intramuscular injections of peanut oil suspensions of dialyzable saline extracts of heart, kidney, liver, or lung tissue from normal rabbits, and after injections of histamine. Activity is maximal by 24 h and normal by 48 h after injection. The LDH isoenzyme patterns of the sera obtained after the administration of the tissue extracts differ n~arkedly from each other and from the LDH isoenzyme patterns of the tissues extracted. They also differ from the serum EDH isoenzyme patterns obtained after the administration of histamine. These results suggest that histamine is not the active substance present in the tissue extracts, that the active materials in the tissue extracts are difFerent from each other, and that the tissue extracts probably do not eflect the release of EDH from the kind of tissue used in their preparation. The active substances in the tissue extracts differ in their heat stabilities, are stable when lyophiliaed, and are adsorbed by Bowex 1 (Cl-) but not by Dowex 50 (H*). These findings suggest that cells contain low molecular weight substances which have the potential of releasing LDH, and presumably other proteins also, from the cells of other tissues. htrsduction The occurrence of abnormal levels of activity of intracellular enzymes in blood serum in certain pathological states has provided a valuable adjunct in the diagnosis of disease (1). Leakage of intracellular enzymes as a consequence of tissue necrosis is considered generally to be a significant factor in the influx of such enzymes into extracellular fluid (2-5). The necrmisleakage mechanism is only partially satisfactory, however, since enzyme release may occur without detectable necrosis (6) and extensive tissue damage may occur without noticeable release of intracellular enzymes into the serum (7, $1Other observations in conflict with the necrosis-leakage mechanism, as a complete explanation of the occurrence of intracellular enzymes in serum, are as follows. Intracellular enzyme activity can decrease in organs other than the damaged one, and n-neasurements of enzyme contents of serum and tissues in conjunction with determined 1%' times of intracellular enzymes in serum in vivo indicate the impossibility in some clinical situations for all the intracellular enzyme in serum to have come from the damaged tissue (9). Furthermore, the transplantation into rodents of carcinomas and sarcomas without detectable lactic acid dehydrogenase (LDH) activity. The liver was proposed as a possible source of the additional enzyme. Consideratiola of the above evidence has led us to investigate the possibility that normal cell constituents released along with the intracellular enzymes as a result of tissue damage may be capable of altering the permeability of undamaged