Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.
Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.
Yi
E S
ES
Department of Pathology, University of California, San Diego School of Medicine, USA.
Lee
H
H
Suh
Y K
YK
Tang
W
W
Qi
M
M
Yin
S
S
Remick
D G
DG
Ulich
T R
TR
D000542:Alveolitis, Extrinsic Allergic / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D011425:Propionibacterium acnes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D014132:Trachea
D018925:Chemokines; D016207:Cytokines; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1