A New Acute Phase Protein Elicited in Mice by Streptolysin O and Other Toxic or Infectious Agents

A new acute phase plasma component has been found in mice exposed to certain toxic materials and pathogenic bacteria. The abnormal component, detected by immunodiffusion employing absorbed antiserum, was chiefly studied in plasma of streptolysin O-treated mice where it appears within 24 hours after intravenous administration of a sublethal dose of the toxin. The new factor is a protein having the electrophoretic mobility of a slow alpha2-globulin. It is devoid of lipid and separate from the streptolysin O inhibitory lipoprotein that is also induced by administration of the streptococcal toxin. The factor, moreover, appears clearly distinct from haptoglobin or C-reactive protein and seems to be a unique type of acute phase protein. Its partial purification by starch block electrophoresis is described. A number of toxic materials other than streptolysin O, i.e. saponin, Cl. welchii phospholipase C (alpha-toxin), and endotoxins, were found to elicit the abnormal protein in mice. Phospholipase A (Crotalus adamanteus venom) and staphylococcal alpha-toxin failed to cause its appearance. Plasma samples of mice acutely infected with Group A streptococci, Staphylococcus aureus or pneumococcus uniformly contained the abnormal component. The significance of this acute phase protein has been considered in relation to the streptolysin O inhibitor and to the acute phase proteins of other animal species. It has been suggested that production of the new component and of the streptolysin O inhibitor may be manifestations of a single process constituting a physiological response to a variety of deleterious agents.