Pulmonary mechanical and immunologic dysfunction in a murine model of AIDS.
Human immunodeficiency virus-infected patients occasionally exhibit alveolar septal wall thickening and decreases in gas diffusion capacity, but the mechanism underlying these abnormalities is unknown. The present study evaluated septal wall thickness and gas exchange properties in a murine model of the acquired immunodeficiency syndrome and determined whether there were alterations in lung lymphocyte deposition and activation that could contribute to changes in respiratory structure and function. Although alveolar septal wall thickness did not differ from control at 1, 2, and 4 wk postimmunosuppressive virus infection, at 8 wk after infection, septal wall thickness was substantially increased. Immunohistochemical evaluation at this time revealed marked increases in the septal wall deposition of fibronectin and collagen type IV. Pulmonary function tests on anesthetized mice with virus-induced septal wall thickening demonstrated that, although total lung capacity, compliance, and functional residual capacity were unaltered, diffusion capacity for carbon monoxide was significantly impaired. A diffuse nonspecific interstitial pneumonitis was present in lungs of immunodeficient mice, and flow cytometry indicated that both lymphocytes and macrophages were activated. Reverse transcriptase-polymerase chain reaction analysis of lung lymphocytes demonstrated enhanced mRNA expression for several cytokines known to affect lung structure. These results show that impaired gas exchange occurs in a murine model of acquired immunodeficiency syndrome and suggest that such alterations may be mediated by elaboration of cytokines from activated lung lymphocytes and macrophages.
Hartsfield
C L
CL
Department of Microbiology and Immunology, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Lipke
D
D
Lai
Y L
YL
Cohen
D A
DA
Gillespie
M N
MN
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000818:Animals; D002248:Carbon Monoxide; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007154:Immune System Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000150:complications / Q000473:pathology; D011653:Pulmonary Diffusing Capacity; D011659:Pulmonary Gas Exchange; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D005353:Fibronectins; D012333:RNA, Messenger; D002248:Carbon Monoxide; D003094:Collagen