Granulocyte/macrophage Colony-stimulating Factor-deficient Mice Show No Major Perturbation of Hematopoiesis but Develop a Characteristic Pulmonary Pathology

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Jun 7

PMID 8202532

Citations 269

Authors

E Stanley

G J Lieschke

D Grail

D Metcalf

G Hodgson

J A Gall

D W Maher

J Cebon

V Sinickas

A R Dunn

Affiliations

Soon will be listed here.

Abstract

Mice homozygous for a disrupted granulocyte/macrophage colony-stimulating factor (GM-CSF) gene develop normally and show no major perturbation of hematopoiesis up to 12 weeks of age. While most GM-CSF-deficient mice are superficially healthy and fertile, all develop abnormal lungs. There is extensive peribronchovascular infiltration with lymphocytes, predominantly B cells. Alveoli contain granular eosinophilic material and lamellar bodies, indicative of surfactant accumulation. There are numerous large intraalveolar phagocytic macrophages. Some mice have subclinical lung infections involving bacterial or fungal organisms, occasionally with focal areas of acute purulent inflammation or lobar pneumonia. Some features of this pathology resemble the human disorder alveolar proteinosis. These observations indicate that GM-CSF is not essential for the maintenance of normal levels of the major types of mature hematopoietic cells and their precursors in blood, marrow, and spleen. However, they implicate GM-CSF as essential for normal pulmonary physiology and resistance to local infection.

Citing Articles

Identification of TNFAIP2 as a unique cellular regulator of CSF-1 receptor activation.

Abdelnaser R, Hiyoshi M, Takahashi N, Eltalkhawy Y, Mizuno H, Kimura S Life Sci Alliance. 2025; 8(5).

PMID: 39939179 PMC: 11821806. DOI: 10.26508/lsa.202403032.

Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.

Popperl P, Stoff M, Beineke A Int J Mol Sci. 2025; 26(1.

PMID: 39796262 PMC: 11721917. DOI: 10.3390/ijms26010407.

Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease.

Tiwari S, Wong W, Moreira M, Pasqualini C, Ginhoux F Nat Rev Immunol. 2024; 25(2):108-124.

PMID: 39333753 DOI: 10.1038/s41577-024-01081-x.

Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis.

Lettieri S, Bonella F, Marando V, Franciosi A, Corsico A, Campo I Eur Respir Rev. 2024; 33(173).

PMID: 39142709 PMC: 11322829. DOI: 10.1183/16000617.0064-2024.

Cancer immunotherapies: A hope for the uncurable?.

Hamdan F, Cerullo V Front Mol Med. 2024; 3:1140977.

PMID: 39086690 PMC: 11285639. DOI: 10.3389/fmmed.2023.1140977.

References

Morse 3rd H, Davidson W, Yetter R, Coffman R . A cell-surface antigen shared by B cells and Ly2+ peripheral T cells. Cell Immunol. 1982; 70(2):311-20. DOI: 10.1016/0008-8749(82)90332-x. View

Rosen S, Castleman B, LIEBOW A . Pulmonary alveolar proteinosis. N Engl J Med. 1958; 258(23):1123-42. DOI: 10.1056/NEJM195806052582301. View

Yelton D, Desaymard C, Scharff M . Use of monoclonal anti-mouse immunoglobulin to detect mouse antibodies. Hybridoma. 1981; 1(1):5-11. DOI: 10.1089/hyb.1.1981.1.5. View

Miyatake S, Otsuka T, Yokota T, Lee F, Arai K . Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes. EMBO J. 1985; 4(10):2561-8. PMC: 554544. DOI: 10.1002/j.1460-2075.1985.tb03971.x. View

Stanley E, Metcalf D, Sobieszczuk P, Gough N, Dunn A . The structure and expression of the murine gene encoding granulocyte-macrophage colony stimulating factor: evidence for utilisation of alternative promoters. EMBO J. 1985; 4(10):2569-73. PMC: 554545. DOI: 10.1002/j.1460-2075.1985.tb03972.x. View

Metcalf D, Begley C, Williamson D, Nice E, De Lamarter J, Mermod J . Hemopoietic responses in mice injected with purified recombinant murine GM-CSF. Exp Hematol. 1987; 15(1):1-9. View

Lang R, Metcalf D, Cuthbertson R, Lyons I, Stanley E, Kelso A . Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell. 1987; 51(4):675-86. DOI: 10.1016/0092-8674(87)90136-x. View

Johnson G, Gonda T, Metcalf D, Hariharan I, Cory S . A lethal myeloproliferative syndrome in mice transplanted with bone marrow cells infected with a retrovirus expressing granulocyte-macrophage colony stimulating factor. EMBO J. 1989; 8(2):441-8. PMC: 400825. DOI: 10.1002/j.1460-2075.1989.tb03396.x. View

Smith S, Lee D, Lacy J, Coleman D . Rat tracheal epithelial cells produce granulocyte/macrophage colony-stimulating factor. Am J Respir Cell Mol Biol. 1990; 2(1):59-68. DOI: 10.1165/ajrcmb/2.1.59. View

10.

Kelso A, Gough N . Differential inhibition by cyclosporin A reveals two pathways for activation of lymphokine synthesis in T cells. Growth Factors. 1989; 1(2):165-77. DOI: 10.3109/08977198909029126. View

11.

Gasson J . Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood. 1991; 77(6):1131-45. View

12.

Tybulewicz V, Crawford C, Jackson P, Bronson R, Mulligan R . Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell. 1991; 65(7):1153-63. DOI: 10.1016/0092-8674(91)90011-m. View

13.

Beck J, Warnock M, Curtis J, Sniezek M, KALTREIDER H, Shellito J . Inflammatory responses to Pneumocystis carinii in mice selectively depleted of helper T lymphocytes. Am J Respir Cell Mol Biol. 1991; 5(2):186-97. DOI: 10.1165/ajrcmb/5.2.186. View

14.

Metcalf D . Lineage commitment of hemopoietic progenitor cells in developing blast cell colonies: influence of colony-stimulating factors. Proc Natl Acad Sci U S A. 1991; 88(24):11310-4. PMC: 53124. DOI: 10.1073/pnas.88.24.11310. View

15.

Nogee L, de Mello D, Dehner L, Colten H . Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med. 1993; 328(6):406-10. DOI: 10.1056/NEJM199302113280606. View

16.

Bilyk N, Holt P . Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med. 1993; 177(6):1773-7. PMC: 2191032. DOI: 10.1084/jem.177.6.1773. View

17.

Metcalf D . Hematopoietic regulators: redundancy or subtlety?. Blood. 1993; 82(12):3515-23. View

18.

Dialynas D, Quan Z, Wall K, Pierres A, Quintans J, Loken M . Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983; 131(5):2445-51. View