Abstract
An animal model of hypersensitivity pneumonitis was developed in order to study the mechanism of early specific allergic response provoked by inhalation provocation test with antigen. Guinea pigs, which were immunized by subcutaneous injection with M. faeni extract antigen emulsified in complete Freund's adjuvant (immunized group) or with only complete Freund's adjuvant (control group), were sacrificed before, and 1, 3, 6, 24, 72 hours and 1 week after an aerosol inhalation challenge with M. faeni extract antigen.
Histopathological findings of the immunized group revealed severe acute bronchiolo-alveolitis consisting of polymorphnuclear cell infiltration, hemorrhage, edema and hyaline membrane degeneration at 6 and 24 hours after the challenge, in contrast to moderate alveolitis with mononuclear cell infiltration observed at 72 hours after the challenge. The number of peripheral blood neutrophils (3hrs: p<0.05, 10 and 24hrs: p<0.01) and serum concentration of immune complexes (24hrs: p<0.05) of immunized group weve significantly increased, and the number of peripheral blood lymphocytes (6hrs: p<0.05, 10 and 24hrs: p<0.01) and serum CH50 (24hrs: p<0.05) of the immunized group were significantly decreased compared with those of the control group. Total cell counts obtained from immunized group by broncho-alveolar lavage (BAL) were strikingly increased at 6-24 hours after the challenge. The analysis of cell populations in BAL fluids of immunized group showed significant increases of the number of neutrophils (6 and 24hrs: p<0.001, 72hrs: p<0.05), alveolar macrophages (72hrs and 1 week: p<0.05) and lymphocytes (72hrs: p<0.01, 1 week: p<0.02) compared with those of the control group. The concentration of IgG/albumin (24hrs: p<0.01, 72hrs: p<0.05) and immune complexes (24hrs: p<0.02) in BAL fluids of immunized group were also significantly elevated compared with those of the control group. Immunofluorecence demonstrated depositions of IgG and/or C3 in the alveolar walls and along the blood vessels of lung sections from almost all immunized animals at 3, 6, 24 and 72 hours after the challenge. In contrast, lung sections from immunized animals before and at 1 week after the challenge, and those from all control animals demonstrated few these depositions. Elevation of body temperature of immunized animals decomplemented by intraperitoneal injection with cobra venom factor just before the challenge (CVF group) was significantly suppressed at 8 hours after the challenge compared with that of immunized but not decomplemented animals (immunized group) (p<0.02). Histopathological findings of hemorrhage, edema and hyaline membrane degeneration demonstrated in the CVF group at 24 hours after the challenge were also less extensive than those demonstrated in the immunized group.
These data suggest, that Type III allergic reaction plays an important role in the mechanism of early specific allergic response provoked by inhalation provocation test in hypersensitivity pneumonitis, especially at 6-24 hours after antigen exposure. The role of Type IV allergic reaction was also considered in this disease, but it seemed to be important at later than 24 hours after antigen exposure.
