The Journal of Immunology, Vol 152, Issue 1 241-249, Copyright © 1994 by American Association of Immunologists

ARTICLES

Production of IL-8 and monocyte chemotactic peptide-1 by peripheral blood monocytes. Disparate responses to phytohemagglutinin and lipopolysaccharide

JM Liebler, SL Kunkel, MD Burdick, TJ Standiford, MW Rolfe and RM Strieter
Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.

The temporal recruitment of leukocytes to a site of inflammation is dependent on a complex interplay of a number of soluble mediators. Recently, two families of chemotactic cytokines have been discovered. The -C-X-C-family, which includes IL-8, appears to recruit neutrophils and lymphocytes. In contrast, the -C-C-family, which includes monocyte chemotactic peptide-1 (MCP-1), appears to recruit predominantly monocytes. Monocytes, after their arrival at a site of inflammation, could further amplify the immune response by secreting IL-8 and MCP-1. We sought to define conditions under which human peripheral blood monocytes produce IL-8 and MCP-1. Using serum-free media, we found that PHA-stimulated monocytes expressed MCP-1 and IL-8 protein and mRNA in a dose-dependent manner. However, the onset of mRNA expression for MCP-1 occurred at least 3 h later than did the onset of IL-8 mRNA expression. IL-8 and MCP-1 gene expression by monocytes appeared to require de novo protein synthesis, in that cycloheximide blocked the expression of mRNA for both IL-8 and MCP-1 in PHA-stimulated cells. However, treatment of monocytes with cycloheximide resulted in the superinduction of IL-8 compared with control monocytes. Monocytes costimulated with PHA and LPS demonstrated enhanced amounts of IL-8 mRNA and protein, but sharply decreased amounts of MCP-1 mRNA and protein. The addition of serum to culture media increased both the constitutive and PHA-induced production of monocyte-derived MCP-1 and IL-8, but had no effect on the inhibition of PHA-stimulated MCP-1 production by LPS. These findings suggest that distinct pathways of activation exist for the production of monocyte-derived IL-8 and MCP-1. The differential expression of these different but related polypeptides may offer a means of control of the type of immune cells that are recruited to a site of inflammation.

This article has been cited by other articles:

				H. R. Zhou, E.-K. Kim, H. Kim, and K. J. Claycombe Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1 Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1153 - E1158. [Abstract] [Full Text] [PDF]

				T. Ikeda, K. Sato, N. Kuwada, T. Matsumura, T. Yamashita, F. Kimura, K. Hatake, K. Ikeda, and K. Motoyoshi Interleukin-10 differently regulates monocyte chemoattractant protein-1 gene expression depending on the environment in a human monoblastic cell line, UG3 J. Leukoc. Biol., December 1, 2002; 72(6): 1198 - 1205. [Abstract] [Full Text] [PDF]

				F. Marti, E. Bertran, M. Llucia, E. Villen, M. Peiro, J. Garcia, and F. Rueda Platelet factor 4 induces human natural killer cells to synthesize and release interleukin-8 J. Leukoc. Biol., September 1, 2002; 72(3): 590 - 597. [Abstract] [Full Text] [PDF]

				J. R. Burke, L. B. Davern, P. L. Stanley, K. R. Gregor, J. Banville, R. Remillard, J. W. Russell, P. J. Brassil, M. R. Witmer, G. Johnson, et al. BMS-229724 Is a Tight-Binding Inhibitor of Cytosolic Phospholipase A2 That Acts at the Lipid/Water Interface and Possesses Anti-Inflammatory Activity in Skin Inflammation Models J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 376 - 385. [Abstract] [Full Text]

				P. Conti, R. C. Barbacane, C. Feliciani, and M. Reale Expression and Secretion of RANTES by Human Peripheral Blood CD4+ Cells are Dependent on the Presence of Monocytes Ann. Clin. Lab. Sci., January 1, 2001; 31(1): 75 - 84. [Abstract] [Full Text] [PDF]

				A. G. Kumar, C. M. Ballantyne, L. H. Michael, G. L. Kukielka, K. A. Youker, M. L. Lindsey, H. K. Hawkins, H. H. Birdsall, C. R. MacKay, G. J. LaRosa, et al. Induction of Monocyte Chemoattractant Protein-1 in the Small Veins of the Ischemic and Reperfused Canine Myocardium Circulation, February 4, 1997; 95(3): 693 - 700. [Abstract] [Full Text]

				T. A. BLAINE, R. N. ROSIER, J. E. PUZAS, R. J. LOONEY, P. R. REYNOLDS, S. D. REYNOLDS, and R. J. O'KEEFE Increased Levels of Tumor Necrosis Factor-{{alpha}} and Interleukin-6 Protein and Messenger RNA in Human Peripheral Blood Monocytes due to Titanium Particles J. Bone Joint Surg. Am., August 1, 1996; 78(8): 1181 - 92. [Abstract] [Full Text]

				M. Takahashi, J.-I. Masuyama, U. Ikeda, T. Kasahara, S.-I. Kitagawa, Y.-I. Takahashi, K. Shimada, and S. Kano Induction of Monocyte Chemoattractant Protein-1 Synthesis in Human Monocytes During Transendothelial Migration In Vitro Circ. Res., May 1, 1995; 76(5): 750 - 757. [Abstract] [Full Text]