We studied various biological activities of crystalline pertussigen and found that in mice as little as 0.5 ng of pertussigen induced hypersensitivity to histamine, 8 to 40 ng induced leukocytosis, 2 ng increased production of insulin, 0.1 ng increased production of immunoglobulin E and immunoglobulin Gl antibodies to hen egg albumin, 9.5 ng increased susceptibility to anaphylactic shock, and 0.5 ng increased the vascular permeability of striated muscle. We also found that in Lewis rats 20 ng of pertussigen promoted the induction of hyperacute experimental allergic encephalomyelitis. Pertussigen given intraperitoneally was toxic to mice at a dose of 546 ng. Treatment of pertussigen with glutaraldehyde eliminated this toxicity. Mice immunized with 1,700 ng of detoxified pertussigen were protected against intracerebral challenge with 3 x 104 viable Bordetella pertussis cells. When as little as 0.5 ng of pertussigen was given intravenously to mice, the increased susceptibility of the animals to histamine could still be detected 84 days later. The biological properties of crystalline pertussigen indicate its similarity to leukocytosis-promoting factor, Islet-activating protein, late-appearing toxic factor, and mouse-protective antigen of B. pertussis.

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a Toxicity = LD5so of histamine given intraperitoneally, expressed as milligrams of histamine base per kilogram of body weight. b J. Munoz, unpublished data. toxin. This reaction was most probably an anaphylactic shock, although it was not recognized as such by Ospeck and Roberts. Parfentjev et al. (186-188) observed a similar phenomenon when they found that mice pretreated with pertussis vaccine died after receiving a denatured nucleoprotein isolated from B. pertussis. This sensitivity was considered to have an immunological basis, but it was not clearly recognized as being associated with anaphylactic shock until Malkiel and Hargis described their observations on the increased susceptibility of B. pertussis-treated mice and rats to actively induced anaphylaxis (121-124). These observations have been confirmed and extended by various workers employing a variety of antigens (100, 154, 205, 223). Furthermore, B. pertussis-treated mice were also seen to become more susceptible to passively induced anaphylaxis (

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