DOI: 10.1152/ajplung.00438.2001. Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure

Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure

10.1152/ajplung.00438.2001

Crossref journal-article

American Physiological Society

American Journal of Physiology-Lung Cellular and Molecular Physiology (24)

Abstract

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.

Bibliography

Homer, R. J., Zheng, T., Chupp, G., He, S., Zhu, Z., Chen, Q., Ma, B., Hite, R. D., Gobran, L. I., Rooney, S. A., & Elias, J. A. (2002). Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure. American Journal of Physiology-Lung Cellular and Molecular Physiology, 283(1), L52âL59.

Authors 11

Robert J. Homer (first)
Tao Zheng (additional)
Geoff Chupp (additional)
Susan He (additional)
Zhou Zhu (additional)
Quingshen Chen (additional)
Bing Ma (additional)
R. Duncan Hite (additional)
Laurice I. Gobran (additional)
Seamus A. Rooney (additional)
Jack A. Elias (additional)

References 50 Referenced 46

10.1016/S0021-9258(18)70226-3 / J Biol Chem by Bartlett GR. (1959)
10.1016/S0146-0005(96)80048-6
10.1152/ajplung.1993.264.6.L543
10.1183/09031936.00.16583100
10.1165/ajrcmb.19.1.2900
10.1172/JCI7325
10.1034/j.1600-065X.2000.917311.x
10.1016/S0091-6749(98)70080-6
10.1042/bj2330111
10.1172/JCI119758
10.1016/S0952-7915(99)80006-5
10.4049/jimmunol.152.5.2421 / J Immunol by Elias JA (1994)
10.4049/jimmunol.164.5.2585
10.1016/S0022-2275(20)37864-0 / J Lipid Res by Gilfillan AM (1983)
10.1152/ajplung.2001.281.6.L1413
10.1074/jbc.275.11.8032
10.1164/ajrccm.158.1.9712061
10.1165/ajrcmb.18.1.2627
10.1164/ajrccm.159.2.9806064
10.1183/09031936.97.10020482
10.1164/ajrccm.159.6.9806145
10.4049/jimmunol.155.5.2688 / J Immunol by Huang SK (1995)
{'key': 'B23', 'first-page': 'A42', 'volume': '161', 'author': 'Hull W', 'year': '2000', 'journal-title': 'Am J Respir Crit Care Med'} / Am J Respir Crit Care Med by Hull W (2000)
10.1152/ajplung.2000.278.1.L75
10.1165/ajrcmb.17.5.2883
10.1164/ajrccm.160.1.9806155
10.1084/jem.190.6.875
10.1038/227680a0
10.1034/j.1600-065X.2000.917308.x
10.1084/jem.194.6.809
{'key': 'B31', 'first-page': 'A515', 'volume': '161', 'author': 'LeVine A', 'year': '2000', 'journal-title': 'Am J Respir Crit Care Med'} / Am J Respir Crit Care Med by LeVine A (2000)
10.1046/j.1365-2222.1997.420885.x
10.1172/JCI10124
10.4049/jimmunol.164.11.5866
10.1165/ajrcmb.15.4.8879185
10.1006/mgme.1998.2722
{'key': 'B37', 'first-page': '439', 'volume': '131', 'author': 'Rooney SA.', 'year': '1985', 'journal-title': 'Am Rev Respir Dis'} / Am Rev Respir Dis by Rooney SA. (1985)
10.1016/0005-2760(88)90014-8
10.1152/ajplung.1999.277.6.L1104
10.1016/0360-3016(82)90092-X
{'key': 'B41', 'first-page': '308', 'volume': '99', 'author': 'Sime PJ', 'year': '2001', 'journal-title': 'Clin Immunol Immunopathol'} / Clin Immunol Immunopathol by Sime PJ (2001)
{'key': 'B42', 'first-page': 'A218', 'volume': '161', 'author': 'Trask BC', 'year': '2000', 'journal-title': 'Am J Respir Crit Care Med'} / Am J Respir Crit Care Med by Trask BC (2000)
10.1002/path.1711750409
10.1073/pnas.100448997
10.1203/00006450-199606000-00002
10.1152/physrev.1997.77.4.931
10.1152/ajplung.1995.268.4.L683
10.1172/JCI10458
10.1177/44.10.8813084
10.1172/JCI5909

Dates

Type	When
Created	10 years, 6 months ago (March 3, 2015, 3:17 p.m.)
Deposited	3 months, 2 weeks ago (May 20, 2025, 1:49 p.m.)
Indexed	3 months, 2 weeks ago (May 20, 2025, 2:10 p.m.)
Issued	23 years, 2 months ago (July 1, 2002)
Published	23 years, 2 months ago (July 1, 2002)
Published Print	23 years, 2 months ago (July 1, 2002)

Funders 0

None

BibTeX

@article{Homer_2002, title={Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure}, volume={283}, ISSN={1522-1504}, url={http://dx.doi.org/10.1152/ajplung.00438.2001}, DOI={10.1152/ajplung.00438.2001}, number={1}, journal={American Journal of Physiology-Lung Cellular and Molecular Physiology}, publisher={American Physiological Society}, author={Homer, Robert J. and Zheng, Tao and Chupp, Geoff and He, Susan and Zhu, Zhou and Chen, Quingshen and Ma, Bing and Hite, R. Duncan and Gobran, Laurice I. and Rooney, Seamus A. and Elias, Jack A.}, year={2002}, month=jul, pages={L52–L59} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        5,
        20
      ]
    ],
    "date-time": "2025-05-20T18:10:03Z",
    "timestamp": 1747764603578,
    "version": "3.41.0"
  },
  "reference-count": 50,
  "publisher": "American Physiological Society",
  "issue": "1",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2002,
        7,
        1
      ]
    ]
  },
  "abstract": "<jats:p>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.</jats:p>",
  "DOI": "10.1152/ajplung.00438.2001",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2015,
        3,
        3
      ]
    ],
    "date-time": "2015-03-03T20:17:43Z",
    "timestamp": 1425413863000
  },
  "page": "L52-L59",
  "source": "Crossref",
  "is-referenced-by-count": 46,
  "title": "Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure",
  "prefix": "10.1152",
  "volume": "283",
  "author": [
    {
      "given": "Robert J.",
      "family": "Homer",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Pathology, Yale University School of Medicine, New Haven 06520;"
        },
        {
          "name": "Pathology and Laboratory Medicine Service, Veterans Affairs Connecticut Healthcare System, West Haven 06516;"
        }
      ]
    },
    {
      "given": "Tao",
      "family": "Zheng",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    },
    {
      "given": "Geoff",
      "family": "Chupp",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    },
    {
      "given": "Susan",
      "family": "He",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    },
    {
      "given": "Zhou",
      "family": "Zhu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    },
    {
      "given": "Quingshen",
      "family": "Chen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    },
    {
      "given": "Bing",
      "family": "Ma",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    },
    {
      "given": "R. Duncan",
      "family": "Hite",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157"
        }
      ]
    },
    {
      "given": "Laurice I.",
      "family": "Gobran",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510; and"
        }
      ]
    },
    {
      "given": "Seamus A.",
      "family": "Rooney",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510; and"
        }
      ]
    },
    {
      "given": "Jack A.",
      "family": "Elias",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine and"
        }
      ]
    }
  ],
  "member": "24",
  "reference": [
    {
      "key": "B1",
      "doi-asserted-by": "crossref",
      "first-page": "466",
      "DOI": "10.1016/S0021-9258(18)70226-3",
      "volume": "234",
      "author": "Bartlett GR.",
      "year": "1959",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "B2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0146-0005(96)80048-6"
    },
    {
      "key": "B3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/ajplung.1993.264.6.L543"
    },
    {
      "key": "B4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1183/09031936.00.16583100"
    },
    {
      "key": "B5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1165/ajrcmb.19.1.2900"
    },
    {
      "key": "B6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI7325"
    },
    {
      "key": "B7",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-065X.2000.917311.x"
    },
    {
      "key": "B8",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0091-6749(98)70080-6"
    },
    {
      "key": "B9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj2330111"
    },
    {
      "key": "B10",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI119758"
    },
    {
      "key": "B11",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0952-7915(99)80006-5"
    },
    {
      "key": "B12",
      "doi-asserted-by": "crossref",
      "first-page": "2421",
      "DOI": "10.4049/jimmunol.152.5.2421",
      "volume": "152",
      "author": "Elias JA",
      "year": "1994",
      "journal-title": "J Immunol"
    },
    {
      "key": "B13",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.164.5.2585"
    },
    {
      "key": "B14",
      "doi-asserted-by": "crossref",
      "first-page": "1651",
      "DOI": "10.1016/S0022-2275(20)37864-0",
      "volume": "24",
      "author": "Gilfillan AM",
      "year": "1983",
      "journal-title": "J Lipid Res"
    },
    {
      "key": "B15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/ajplung.2001.281.6.L1413"
    },
    {
      "key": "B16",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.275.11.8032"
    },
    {
      "key": "B17",
      "doi-asserted-by": "publisher",
      "DOI": "10.1164/ajrccm.158.1.9712061"
    },
    {
      "key": "B18",
      "doi-asserted-by": "publisher",
      "DOI": "10.1165/ajrcmb.18.1.2627"
    },
    {
      "key": "B19",
      "doi-asserted-by": "publisher",
      "DOI": "10.1164/ajrccm.159.2.9806064"
    },
    {
      "key": "B20",
      "doi-asserted-by": "publisher",
      "DOI": "10.1183/09031936.97.10020482"
    },
    {
      "key": "B21",
      "doi-asserted-by": "publisher",
      "DOI": "10.1164/ajrccm.159.6.9806145"
    },
    {
      "key": "B22",
      "doi-asserted-by": "crossref",
      "first-page": "2688",
      "DOI": "10.4049/jimmunol.155.5.2688",
      "volume": "155",
      "author": "Huang SK",
      "year": "1995",
      "journal-title": "J Immunol"
    },
    {
      "key": "B23",
      "first-page": "A42",
      "volume": "161",
      "author": "Hull W",
      "year": "2000",
      "journal-title": "Am J Respir Crit Care Med"
    },
    {
      "key": "B24",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/ajplung.2000.278.1.L75"
    },
    {
      "key": "B25",
      "doi-asserted-by": "publisher",
      "DOI": "10.1165/ajrcmb.17.5.2883"
    },
    {
      "key": "B26",
      "doi-asserted-by": "publisher",
      "DOI": "10.1164/ajrccm.160.1.9806155"
    },
    {
      "key": "B27",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.190.6.875"
    },
    {
      "key": "B28",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/227680a0"
    },
    {
      "key": "B29",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-065X.2000.917308.x"
    },
    {
      "key": "B30",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.194.6.809"
    },
    {
      "key": "B31",
      "first-page": "A515",
      "volume": "161",
      "author": "LeVine A",
      "year": "2000",
      "journal-title": "Am J Respir Crit Care Med"
    },
    {
      "key": "B32",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2222.1997.420885.x"
    },
    {
      "key": "B33",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI10124"
    },
    {
      "key": "B34",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.164.11.5866"
    },
    {
      "key": "B35",
      "doi-asserted-by": "publisher",
      "DOI": "10.1165/ajrcmb.15.4.8879185"
    },
    {
      "key": "B36",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/mgme.1998.2722"
    },
    {
      "key": "B37",
      "first-page": "439",
      "volume": "131",
      "author": "Rooney SA.",
      "year": "1985",
      "journal-title": "Am Rev Respir Dis"
    },
    {
      "key": "B38",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0005-2760(88)90014-8"
    },
    {
      "key": "B39",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/ajplung.1999.277.6.L1104"
    },
    {
      "key": "B40",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0360-3016(82)90092-X"
    },
    {
      "key": "B41",
      "first-page": "308",
      "volume": "99",
      "author": "Sime PJ",
      "year": "2001",
      "journal-title": "Clin Immunol Immunopathol"
    },
    {
      "key": "B42",
      "first-page": "A218",
      "volume": "161",
      "author": "Trask BC",
      "year": "2000",
      "journal-title": "Am J Respir Crit Care Med"
    },
    {
      "key": "B43",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/path.1711750409"
    },
    {
      "key": "B44",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.100448997"
    },
    {
      "key": "B45",
      "doi-asserted-by": "publisher",
      "DOI": "10.1203/00006450-199606000-00002"
    },
    {
      "key": "B46",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/physrev.1997.77.4.931"
    },
    {
      "key": "B47",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/ajplung.1995.268.4.L683"
    },
    {
      "key": "B48",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI10458"
    },
    {
      "key": "B49",
      "doi-asserted-by": "publisher",
      "DOI": "10.1177/44.10.8813084"
    },
    {
      "key": "B50",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI5909"
    }
  ],
  "container-title": "American Journal of Physiology-Lung Cellular and Molecular Physiology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.physiology.org/doi/pdf/10.1152/ajplung.00438.2001",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2025,
        5,
        20
      ]
    ],
    "date-time": "2025-05-20T17:49:01Z",
    "timestamp": 1747763341000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.physiology.org/doi/10.1152/ajplung.00438.2001"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2002,
        7,
        1
      ]
    ]
  },
  "references-count": 50,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          2002,
          7,
          1
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1152/ajplung.00438.2001"
  ],
  "URL": "http://dx.doi.org/10.1152/ajplung.00438.2001",
  "relation": {},
  "ISSN": [
    "1040-0605",
    "1522-1504"
  ],
  "subject": [],
  "container-title-short": "American Journal of Physiology-Lung Cellular and Molecular Physiology",
  "published": {
    "date-parts": [
      [
        2002,
        7,
        1
      ]
    ]
  }
}