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. 1993 Oct;143(4):1009–1015.

Polymorphonuclear leukocytes as a significant source of tumor necrosis factor-alpha in endotoxin-challenged lung tissue.

Z Xing 1, H Kirpalani 1, D Torry 1, M Jordana 1, J Gauldie 1
PMCID: PMC1887070  PMID: 8213996

Abstract

The kinetic expression and potential cellular source of tumor necrosis factor-alpha (TNF-alpha) in lipopolysaccharide-(LPS) induced acute lung inflammation was investigated using a rat model by Northern blot analysis, in situ hybridization and immunohistochemistry. LPS induced a polymorphonuclear leukocyte infiltrate in the lung that peaked between 6 and 24 hours. TNF-alpha messenger (m)RNA was strongly induced by LPS in whole lung tissues shown by Northern analysis. Both alveolar macrophages and polymorphonuclear leukocytes (PMNs), purified from bronchoalveolar lavage fluids of LPS-treated rats, were shown to express TNF-alpha mRNA by Northern analysis. However, PMNs displayed several times more TNF-alpha mRNA, relative to actin mRNA, than alveolar macrophages at 6 and 12 hours. By in situ hybridization, most of the cells positive for TNF-alpha mRNA at 6 and 12 hours seemed to be PMNs located within the tissue near bronchioles or vessels. By immunohistochemistry, TNF-alpha protein was localized mainly to alveolar macrophages at early times (1 to 3 hours) after LPS challenge, and thereafter, PMNs seemed to be the predominant source of TNF-alpha protein as more than 90% of total intraalveolar positive cells at 6 and 12 hours were PMN. Thus, our data provide the first in vivo evidence that PMNs can serve as a significant source of TNF-alpha at sites of acute inflammation.

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Selected References

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  1. Bazzoni F., Cassatella M. A., Laudanna C., Rossi F. Phagocytosis of opsonized yeast induces tumor necrosis factor-alpha mRNA accumulation and protein release by human polymorphonuclear leukocytes. J Leukoc Biol. 1991 Sep;50(3):223–228. doi: 10.1002/jlb.50.3.223. [DOI] [PubMed] [Google Scholar]
  2. Becker S., Devlin R. B., Haskill J. S. Differential production of tumor necrosis factor, macrophage colony stimulating factor, and interleukin 1 by human alveolar macrophages. J Leukoc Biol. 1989 Apr;45(4):353–361. [PubMed] [Google Scholar]
  3. Brigham K. L., Meyrick B. Endotoxin and lung injury. Am Rev Respir Dis. 1986 May;133(5):913–927. [PubMed] [Google Scholar]
  4. Chensue S. W., Remick D. G., Shmyr-Forsch C., Beals T. F., Kunkel S. L. Immunohistochemical demonstration of cytoplasmic and membrane-associated tumor necrosis factor in murine macrophages. Am J Pathol. 1988 Dec;133(3):564–572. [PMC free article] [PubMed] [Google Scholar]
  5. Cicco N. A., Lindemann A., Content J., Vandenbussche P., Lübbert M., Gauss J., Mertelsmann R., Herrmann F. Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. Blood. 1990 May 15;75(10):2049–2052. [PubMed] [Google Scholar]
  6. Djeu J. Y., Serbousek D., Blanchard D. K. Release of tumor necrosis factor by human polymorphonuclear leukocytes. Blood. 1990 Oct 1;76(7):1405–1409. [PubMed] [Google Scholar]
  7. Dubravec D. B., Spriggs D. R., Mannick J. A., Rodrick M. L. Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6758–6761. doi: 10.1073/pnas.87.17.6758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lloyd A. R., Oppenheim J. J. Poly's lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol Today. 1992 May;13(5):169–172. doi: 10.1016/0167-5699(92)90121-M. [DOI] [PubMed] [Google Scholar]
  9. Marucha P. T., Zeff R. A., Kreutzer D. L. Cytokine regulation of IL-1 beta gene expression in the human polymorphonuclear leukocyte. J Immunol. 1990 Nov 1;145(9):2932–2937. [PubMed] [Google Scholar]
  10. Nelson S., Bagby G. J., Bainton B. G., Wilson L. A., Thompson J. J., Summer W. R. Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis. 1989 Feb;159(2):189–194. doi: 10.1093/infdis/159.2.189. [DOI] [PubMed] [Google Scholar]
  11. Ohno I., Lea R. G., Flanders K. C., Clark D. A., Banwatt D., Dolovich J., Denburg J., Harley C. B., Gauldie J., Jordana M. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest. 1992 May;89(5):1662–1668. doi: 10.1172/JCI115764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ohno I., Lea R., Finotto S., Marshall J., Denburg J., Dolovich J., Gauldie J., Jordana M. Granulocyte/macrophage colony-stimulating factor (GM-CSF) gene expression by eosinophils in nasal polyposis. Am J Respir Cell Mol Biol. 1991 Dec;5(6):505–510. doi: 10.1165/ajrcmb/5.6.505. [DOI] [PubMed] [Google Scholar]
  13. Palma C., Cassone A., Serbousek D., Pearson C. A., Djeu J. Y. Lactoferrin release and interleukin-1, interleukin-6, and tumor necrosis factor production by human polymorphonuclear cells stimulated by various lipopolysaccharides: relationship to growth inhibition of Candida albicans. Infect Immun. 1992 Nov;60(11):4604–4611. doi: 10.1128/iai.60.11.4604-4611.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pauwels R. A., Kips J. C., Peleman R. A., Van Der Straeten M. E. The effect of endotoxin inhalation on airway responsiveness and cellular influx in rats. Am Rev Respir Dis. 1990 Mar;141(3):540–545. doi: 10.1164/ajrccm/141.3.540. [DOI] [PubMed] [Google Scholar]
  15. Pennica D., Hayflick J. S., Bringman T. S., Palladino M. A., Goeddel D. V. Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6060–6064. doi: 10.1073/pnas.82.18.6060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Remick D. G. Significance of in vivo detection of tumor necrosis factor. Lab Invest. 1991 Sep;65(3):259–261. [PubMed] [Google Scholar]
  17. Rolfe M. W., Kunkel S. L., Standiford T. J., Chensue S. W., Allen R. M., Evanoff H. L., Phan S. H., Strieter R. M. Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking. Am J Respir Cell Mol Biol. 1991 Nov;5(5):493–501. doi: 10.1165/ajrcmb/5.5.493. [DOI] [PubMed] [Google Scholar]
  18. Strieter R. M., Kasahara K., Allen R. M., Standiford T. J., Rolfe M. W., Becker F. S., Chensue S. W., Kunkel S. L. Cytokine-induced neutrophil-derived interleukin-8. Am J Pathol. 1992 Aug;141(2):397–407. [PMC free article] [PubMed] [Google Scholar]
  19. Tracey K. J., Lowry S. F., Cerami A. Cachetin/TNF-alpha in septic shock and septic adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Dec;138(6):1377–1379. doi: 10.1164/ajrccm/138.6.1377. [DOI] [PubMed] [Google Scholar]
  20. Ulich T. R., Guo K., Yin S., del Castillo J., Yi E. S., Thompson R. C., Eisenberg S. P. Endotoxin-induced cytokine gene expression in vivo. IV. Expression of interleukin-1 alpha/beta and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation. Am J Pathol. 1992 Jul;141(1):61–68. [PMC free article] [PubMed] [Google Scholar]
  21. Ulich T. R., Watson L. R., Yin S. M., Guo K. Z., Wang P., Thang H., del Castillo J. The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate. Am J Pathol. 1991 Jun;138(6):1485–1496. [PMC free article] [PubMed] [Google Scholar]
  22. Williams J. H., Jr, Patel S. K., Hatakeyama D., Arian R., Guo K., Hickey T. J., Liao S. Y., Ulich T. R. Activated pulmonary vascular neutrophils as early mediators of endotoxin-induced lung inflammation. Am J Respir Cell Mol Biol. 1993 Feb;8(2):134–144. doi: 10.1165/ajrcmb/8.2.134. [DOI] [PubMed] [Google Scholar]
  23. Xing Z., Jordana M., Gauldie J. IL-1 beta and IL-6 gene expression in alveolar macrophages: modulation by extracellular matrices. Am J Physiol. 1992 May;262(5 Pt 1):L600–L605. doi: 10.1152/ajplung.1992.262.5.L600. [DOI] [PubMed] [Google Scholar]
  24. Xing Z., Ohtoshi T., Ralph P., Gauldie J., Jordana M. Human upper airway structural cell-derived cytokines support human peripheral blood monocyte survival: a potential mechanism for monocyte/macrophage accumulation in the tissue. Am J Respir Cell Mol Biol. 1992 Feb;6(2):212–218. doi: 10.1165/ajrcmb/6.2.212. [DOI] [PubMed] [Google Scholar]
  25. de Rochemonteix-Galve B., Marchat-Amoruso B., Dayer J. M., Rylander R. Tumor necrosis factor and interleukin-1 activities in free lung cells after single and repeated inhalation of bacterial endotoxin. Infect Immun. 1991 Oct;59(10):3646–3650. doi: 10.1128/iai.59.10.3646-3650.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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