HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal 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 Weinberg, J. B. Articles by Hibbs, J. B. Search for Related Content PubMed Articles by Weinberg, J. B. Articles by Hibbs, J. B., Jr.

Characterization of the Effects of Endotoxin on Macrophage Tumor Cell Killing¹

From the Veterans Administration Hospital and Department of Medicine, Divisions of Hematology-Oncology and Infectious Diseases, University of Utah Medical Center, Salt Lake City, Utah 84148

Abstract

These studies demonstrate the potent effect of LPS on the induction of macrophage-mediated tumor cell killing and show, by using pure populations of cloned macrophages as effector cells, that LPS can act in the complete absence of contaminating lymphocytes. Macrophage differentiation toward the tumoricidal state parallels the responsiveness of macrophages to LPS. Normal macrophages will not kill even in the presence of 10 µg/ml LPS; peptone-induced normal macrophages (stimulated macrophages) are made tumoricidal by 500 mg/ml LPS; and nontumoricidal BCG-activated macrophages are made to kill tumor cells by 0.5 to 1.0 ng/ml LPS. The LPS effect is reproduced by lipid A. The effect is abolished by alkaline treatment of LPS or by the presence of polymyxin B. Nontumoricidal BCG-activated macrophages from the lipid A-nonresponder mouse strain C3H/HeJ require 250 times more LPS to become tumoricidal than do nontumoricidal BCG-activated macrophages from the C3H/HeN strain. LPS acts synergistically with MAF-rich peritoneal cell supernatants in causing macrophages to kill tumor cells. Although LPS can elicit MAF production by lymphocytes, it can also act directly on cells of lymphocyte-free macrophage colonies to render them tumoricidal. Reagents are frequently contaminated with LPS, and unless this is noted, valid interpretation of experiments investigating macrophage tumor cell killing is difficult. Means of detecting, detoxifying, and eliminating the LPS of experimental agents are discussed.

Footnotes

¹ This work was supported by the Veteran's Administration, Washington, D. C., and by National Institutes of Health Grants CA14045 and CA15811.

This article has been cited by other articles:

				S. W. Fox, K. Fuller, K. E. Bayley, J. M. Lean, and T. J. Chambers TGF-{beta}1 and IFN-{gamma} Direct Macrophage Activation by TNF-{alpha} to Osteoclastic or Cytocidal Phenotype J. Immunol., November 1, 2000; 165(9): 4957 - 4963. [Abstract] [Full Text] [PDF]

				C. D. Mills, K. Kincaid, J. M. Alt, M. J. Heilman, and A. M. Hill M-1/M-2 Macrophages and the Th1/Th2 Paradigm J. Immunol., June 15, 2000; 164(12): 6166 - 6173. [Abstract] [Full Text] [PDF]

				J. Hibbs Jr, R. Taintor, and Z Vavrin Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite Science, January 23, 1987; 235(4787): 473 - 476. [Abstract] [PDF]

				K. Grabstein, D. Urdal, R. Tushinski, D. Mochizuki, V. Price, M. Cantrell, S Gillis, and P. Conlon Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor Science, April 25, 1986; 232(4749): 506 - 508. [Abstract] [PDF]

				J. Weinberg Tumor cell killing by phorbol ester--differentiated human leukemia cells Science, August 7, 1981; 213(4508): 655 - 657. [Abstract] [PDF]