This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomassen, M. J. Articles by Ahmad, M. Search for Related Content PubMed PubMed Citation Articles by Thomassen, M. J. Articles by Ahmad, M.

Differential Effect of Recombinant Granulocyte Macrophage Colony-stimulating Factor on Human Monocytes and Alveolar Macrophages¹

Departments of Pulmonary Disease [M. J. T., H. P. W., M. A.], and Immunopathology [B. P. B.] and the Research Institute [M. J. T., D. R.], The Cleveland Clinic Foundation, Cleveland, Ohio 44195-5038

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pluripotent cytokine, on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [³H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500–5000 units/ml) of recombinant GM-CSF indicated dramatic differences between cytotoxicity of alveolar macrophages and blood monocytes. Macrophages exhibited significant (P < 0.01) tumoricidal activity at all GM-CSF doses tested. In contrast, monocytes showed no significant tumoricidal activity at 500 units/ml and significantly (P < 0.01) less activity than alveolar macrophages at doses of 1000–5000 units/ml. Maximal activity in alveolar macrophages occurred 72–96 h after exposure to 1000–5000 units/ml GM-CSF. Tumoricidal activity may be related to the state of maturation, because monocytes matured in vitro for 7 days displayed enhanced tumoricidal activity after GM-CSF exposure. Tumor necrosis factor and interleukin 1ß were measured in supernatant fluids of 24-h GM-CSF-treated cells. No significant increase in either cytokine was detected after GM-CSF treatment of alveolar macrophages. Monocyte interleukin 1ß secretion was not enhanced by GM-CSF; however, tumor necrosis factor secretion was enhanced in some donors (three of five). Superoxide anion production of alveolar macrophages was not enhanced by GM-CSF. These data suggest that alveolar macrophage tumoricidal activity is induced by GM-CSF and is not dependent on oxidative metabolism or secreted forms of interleukin 1ß or tumor necrosis factor .

¹ This work was supported by NIH Grant HL 36078, a grant from the Cuyahoga County Unit of the American Cancer Society, and the DeBartolo Scholar Award.

² To whom requests for reprints should be addressed.

Received 12/29/88. Revised 2/27/89. Accepted 4/25/89.

This article has been cited by other articles:

				B. M. Rotoli, V. Dall'Asta, A. Barilli, R. D'Ippolito, A. Tipa, D. Olivieri, G. C. Gazzola, and O. Bussolati Alveolar Macrophages from Normal Subjects Lack the NOS-Related System y+ for Arginine Transport Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 105 - 112. [Abstract] [Full Text] [PDF]

				L. E. Spitler, M. L. Grossbard, M. S. Ernstoff, G. Silver, M. Jacobs, F. A. Hayes, and S. J. Soong Adjuvant Therapy of Stage III and IV Malignant Melanoma Using Granulocyte-Macrophage Colony-Stimulating Factor J. Clin. Oncol., April 1, 2000; 18(8): 1614 - 1621. [Abstract] [Full Text] [PDF]

				C.L. Scott, D.A. Hughes, D. Cary, N.A. Nicola, C.G. Begley, and L. Robb Functional Analysis of Mature Hematopoietic Cells From Mice Lacking the beta c Chain of the Granulocyte-Macrophage Colony-Stimulating Factor Receptor Blood, December 1, 1998; 92(11): 4119 - 4127. [Abstract] [Full Text] [PDF]

				J. F. Seymour, C. G. Begley, U. Dirksen, J. J. Presneill, N. A. Nicola, P. E. Moore, O. D. Schoch, P. vanAsperen, B. Roth, S. Burdach, et al. Attenuated Hematopoietic Response to Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Acquired Pulmonary Alveolar Proteinosis Blood, October 15, 1998; 92(8): 2657 - 2667. [Abstract] [Full Text] [PDF]

				G. C. BALDWIN, D. P. TASHKIN, D. M. BUCKLEY, A. N. PARK, S. M. DUBINETT, and M. D. ROTH Marijuana and Cocaine Impair Alveolar Macrophage Function and Cytokine Production Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1606 - 1613. [Abstract] [Full Text]