Pulmonary Damage Induced in Mice by a Monoclonal Antibody to Proteins Associated with Pig Pulmonary Surfactant

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Abstract
Severe pulmonary damage was induced in mice inoculated with hybridomas (8B5E) secreting a monoclonal antibody to the 15,000-dalton protein associated with pig pulmonary surfactant. These mice exhibited severe respiratory distress starting 8-9 days after inoculation and died. Microscopically, lungs were airless and congested with hyaline membrane formation in patent terminal airways. Purified antibody from this hybridoma also induced similar damage in mouse lungs. However, neither hybridomas (1B64) nor purified antibody, which is specific to pig 35,000-dalton protein but not to the mouse counterpart, induced these changes. Electron microscopically, many unexpandeld lamellar bodies were seen floating in the edema fluid in these damaged lungs, and fragmentary lipid membranes were found in the electron dense material around these lamellar bodies, suggesting distintegration of these structures. Alveolar epithelial cells were desquamated, leaving the basement membranes bare, and mouse C3 was demonstrated in the damaged lungs. This low-molecular-weight protein of mouse surfactant cross-reacted with this antibody in the immunoblotting method, and the antigen was locacted in the inclusions of alveolar wall cells. These observations indicate that this low-molecular-weight protein of mouse surfactant has an antigenic structure similar to pig surfactant protein and that antigen-antibody complex formation may have triffered the damage of the lungs through inactivation of surfactant and induction of immunological tissue damage.

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