PERTUSSIS HEAT LABILE TOXIN (HLT)--ISOLATION AND CHARACTERIZATION

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Bordetella pertussis produces several protein toxins including pertussis toxin (see project Z01 HD 1302) and dermonecrotic toxin or heat labile toxin (HLT). HLT, when injected subcutaneously into suckling mice, results in a local pronounced hemorrhagic lesion. The extent, localization, and nature of this toxin-induced injury suggests HLT contributes to the pathogenesis of B. pertussis. Conditions for assay of the toxin, using the suckling mouse model, have been established. Homogeneous preparations of HLT have been obtained and it has been established that the toxin is a single polypeptide chain with a molecular weight of about 150,000. The purified toxin has been used to produce antibodies. These antibodies have been used to document the purity of current toxin preparation. In addition, they neutralize toxic activity and high titer sera (1/20,000) have been obtained from immunized rabbits. Passive immunization of mice with HLT directed antibody protects mice against challenge with live B. pertussis suggesting that HLT may serve as a protective antigen. To investigate this possibility in greater detail, monoclonal antibodies to HLT are being produced. The toxicity of HLT is poorly understood and more detailed information establishing its role in pathogenesis is needed. Preliminary studies in which purified HLT was injected into mice indicate that the effects of the toxin are broad and histologic changes affect tissues such as spleen, liver, marrow, and thymus. Understanding of the pathologic changes in these tissues should contribute to elucidation of its mechanism of action and role in disease.