Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure.
Interleukin (IL)-13, a key mediator of Th2-mediated immunity, contributes to the pathogenesis of asthma and other pulmonary diseases via its ability to generate fibrosis, mucus metaplasia, eosinophilic inflammation, and airway hyperresponsiveness. In these studies, we compared surfactant accumulation in wild-type mice and mice in which IL-13 was overexpressed in the lung. When compared with littermate controls, transgenic animals showed alveolar type II cell hypertrophy under light and electron microscopy. Over time, their alveoli also filled with surfactant in a pulmonary alveolar proteinosis pattern. At the same time, prominent interstitial fibrosis occurs. Bronchoalveolar lavage fluid from these mice had a three- to sixfold increase in surfactant phospholipids. Surfactant proteins (SP)-A, -B, and -C showed two- to threefold increases, whereas SP-D increased 70-fold. These results indicate that IL-13 is a potent stimulator of surfactant phospholipid and surfactant accumulation in the lung. IL-13 may therefore play a central role in the broad range of chronic pulmonary conditions in which fibrosis, type II cell hypertrophy, and surfactant accumulation occur.
Homer
Robert J
RJ
Department of Pathology, Yale University School of Medicine, New Haven 06520, USA. Robert.Homer@yale.edu
Zheng
Tao
T
Chupp
Geoff
G
He
Susan
S
Zhu
Zhou
Z
Chen
Quingshen
Q
Ma
Bing
B
Hite
R Duncan
RD
Gobran
Laurice I
LI
Rooney
Seamus A
SA
Elias
Jack A
JA
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006984:Hypertrophy; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011510:Proteolipids / Q000032:analysis / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000473:pathology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D018793:Interleukin-13; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger