Comparison of the evolving histopathology of early and late cutaneous and asthmatic responses in rabbits after a single antigen challenge

Behrens, B.L.; Clark, R.A.; Presley, D.M.; Graves, J.P.; Feldsien, D.C.; Larsen, G.L.

Laboratory Investigation; A Journal of Technical Methods and Pathology 56(1): 101-113


ISSN/ISBN: 0023-6837
PMID: 3540448
Accession: 005014326

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Histopathologic changes during the immediate cutaneous response (ICR) and late cutaneous response (LCR) to antigen challenge in allergic humans include dermal edema in the ICR (15 to 30 minutes) followed by increasing cellular infiltration in the LCR (6 hours and more). No description of the evolving histopathologic changes that occur during an immediate asthmatic response (IAR) followed by a late asthmatic response (LAR) exists in either clinical studies or animal models. We examined cutaneous and pulmonary histopathology at 1/2, 6, 24, and 48 hours as well as 7 days after simultaneous intradermal and aerosol antigen challenge of rabbits immunized with Alternaria tenuis extract. Nonimmunized rabbits challenged with Alternaria tenuis extract and immunized rabbits challenged with normal saline served as controls. Immediate wheal and flare responses followed by a LCR were seen in immunized but not control animals. Pulmonary function tests documented immediate and LAR in immunized but not control animals. Pulmonary function test documented immediate and LAR in immunized but not control animals. Thirty minutes after antigen challenge of sensitized animals (ICR and IAR), both dermal sites and large airway submucosal sites had interstitial edema and vessel dilatation while small airways were essentially normal. At 6 hours after challenge, the dermal and large airway submucosal sites of immune animals (LCR and LAR) demonstrated a moderate mixed leukocyte infiltrate as well as residual edema. Additionally, bronchioles and pulmonary vessel adventitia from these responding animals had an intense and widespread leukocyte infiltration. At 24 and 48 hours, immune challenged animals but not controls had a marked mixed cellular infiltrate near skin vessels and near the bronchioles and pulmonary vessels with little or no residual interstitial edema. At 7 days, three of four animals showed resolution of the inflammation substantiated these quantitative observations and demonstrated that the granulocytes around airways of immune rabbits were a mixture of neutrophils and eosinophils at 6 hours, but were predominantly eosinophils at 48 hours. Immunofluorescent studies of skin and lung tissue did not demonstrate any granular or linear deposition of immunoglobulin or complement at the sites of inflammation, however, fibrin deposition was noted in the skin and lungs of immune rabbits. These observations show that immunized rabbits challenged with antigen develop cutaneous and pulmonary inflammation. Since the cutaneous pathology in challenged immune rabbits is similar to the histopathology of human ICR and LCR, the pathology in the airways in the rabbit model of the IAR and LAR may be similar to that found in human asthma.