Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5A and FMLP as second signals

doi:10.1084/jem.167.4.1281

This Article

Full Text (PDF, 919K)

Alert me when this article is cited

Citation Map

Services

Email this article

Similar articles in this journal

Similar articles in PubMed

Alert me to new content in the JEM

Download to citation manager

Citing Articles

Citing Articles via HighWire

Citing Articles via CrossRef

Citing Articles via Google Scholar

Google Scholar

Articles by Dahinden, C. A.

Articles by de Weck, A. L.

Search for Related Content

PubMed

PubMed Citation

Articles by Dahinden, C. A.

Articles by de Weck, A. L.

Pubmed/NCBI databases

Compound via MeSH
Substance via MeSH

Social Bookmarking

What's this?

ARTICLES

Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5A and FMLP as second signals

CA Dahinden, J Zingg, FE Maly and AL de Weck
Institute of Clinical Immunology, Inselspital, Bern, Switzerland.

Neutrophils (PMN) preincubated with recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) for 2 h and then stimulated with the chemotactic factors, C5a or FMLP, produce substantial amounts of the lipoxygenase products 5-Hete, LTB4, and omega-oxidised LTB4 metabolites (4.36 +/- 0.95 (SEM) pM (n = 21) LTB4 and LTB4 metabolites/10(6) PMN). No lipoxygenase metabolites are detected by HPLC and RIA if purified PMN are stimulated by either GM- CSF or chemotactic factors in the absence of exogenous arachidonate. The priming effect of GM-CSF upon chemotactic factor induced generation of lipid mediators is a relatively slow process, clearly evident after 1 h and optimal after 2 h. Leukotriene generation is measurable with 0.8 U GM-CSF/10(6) PMN and is maximal with 80 U (10(-11)-10(-9) M). Upon activation of primed PMN with chemotactic factors, leukotriene synthesis is induced very rapidly. Already 2.5 min after activation the major lipoxygenase metabolites present are 20-OH LTB4 and 20-COOH LTB4. Our study shows that the synthesis of lipoxygenase metabolites from endogeneous AA can be initiated in PMN through receptor mediated processes by the appropriately timed combination of biological soluble inflammatory mediator peptides. Furthermore, these results indicate that GM-CSF not only enhances effector cell functions but can qualitatively change the mediator profile formed after activation with a second triggering signal. Such a mechanism might be important in amplifying inflammatory responses. Alternatively, lipid mediators formed might also have an intracellular or autocoid role and be responsible for the enhancement of other PMN functions like oxygen radical release.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Lindner, S. C., Kohl, U., Maier, T. J., Steinhilber, D., Sorg, B. L. (2009). TLR2 ligands augment cPLA2{alpha} activity and lead to enhanced leukotriene release in human monocytes. J. Leukoc. Biol. 86: 389-399 [Abstract] [Full Text]
Daryadel, A., Yousefi, S., Troi, D., Schmid, I., Schmidt-Mende, J., Mordasini, C., Dahinden, C. A., Ziemiecki, A., Simon, H.-U. (2009). RhoH/TTF Negatively Regulates Leukotriene Production in Neutrophils. J. Immunol. 182: 6527-6532 [Abstract] [Full Text]
Ferrari, D., la Sala, A., Panther, E., Norgauer, J., Di Virgilio, F., Idzko, M. (2006). Activation of human eosinophils via P2 receptors: novel findings and future perspectives. J. Leukoc. Biol. 79: 7-15 [Abstract] [Full Text]
Kobayashi, S. D., Voyich, J. M., Whitney, A. R., DeLeo, F. R. (2005). Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor. J. Leukoc. Biol. 78: 1408-1418 [Abstract] [Full Text]
Huang, L., Zhao, A., Wong, F., Ayala, J. M., Struthers, M., Ujjainwalla, F., Wright, S. D., Springer, M. S., Evans, J., Cui, J. (2004). Leukotriene B4 Strongly Increases Monocyte Chemoattractant Protein-1 in Human Monocytes. Arterioscler. Thromb. Vasc. Bio. 24: 1783-1788 [Abstract] [Full Text]
Simon, H.-U., Weber, M., Becker, E., Zilberman, Y., Blaser, K., Levi-Schaffer, F. (2000). Eosinophils Maintain Their Capacity to Signal and Release Eosinophil Cationic Protein Upon Repetitive Stimulation with the Same Agonist. J. Immunol. 165: 4069-4075 [Abstract] [Full Text]
FLAMAND, N., BOUDREAULT, S., PICARD, S., AUSTIN, M., SURETTE, M. E., PLANTE, H., KRUMP, E., VALLEE, M.-J., GILBERT, C., NACCACHE, P., LAVIOLETTE, M., BORGEAT, P. (2000). Adenosine, a Potent Natural Suppressor of Arachidonic Acid Release and Leukotriene Biosynthesis in Human Neutrophils. Am. J. Respir. Crit. Care Med. 161: S88-94 [Full Text]
Surette, M. E., Krump, E., Picard, S., Borgeat, P. (1999). Activation of Leukotriene Synthesis in Human Neutrophils by Exogenous Arachidonic Acid: Inhibition by Adenosine A2a Receptor Agonists and Crucial Role of Autocrine Activation by Leukotriene B4. Mol. Pharmacol. 56: 1055-1062 [Abstract] [Full Text]
Meddows-Taylor, S., Martin, D. J., Tiemessen, C. T. (1999). Impaired Interleukin-8-Induced Degranulation of Polymorphonuclear Neutrophils from Human Immunodeficiency Virus Type 1-Infected Individuals. CVI 6: 345-351 [Abstract] [Full Text]
Surette, M. E., Dallaire, N., Jean, N., Picard, S., Borgeat, P. (1998). Mechanisms of the priming effect of lipopolysaccharides on the biosynthesis of leukotriene B4 in chemotactic peptide-stimulated human neutrophils. FASEB J. 12: 1521-1531 [Abstract] [Full Text]
Daniels, I., Lindsay, M. A., Keany, C. I.�C., Burden, R. P., Fletcher, J., Haynes, A. P. (1998). Role of Arachidonic Acid and Its Metabolites in the Priming of NADPH Oxidase in Human Polymorphonuclear Leukocytes by Peritoneal Dialysis Effluent. CVI 5: 683-689 [Abstract] [Full Text]
Gosselin, J., Borgeat, P. (1997). Epstein-Barr Virus Modulates 5-Lipoxygenase Product Synthesis in Human Peripheral Blood Mononuclear Cells. Blood 89: 2122-2130 [Abstract] [Full Text]
Brizzi, M. F., Aronica, M. G., Rosso, A., Bagnara, G. P., Yarden, Y., Pegoraro, L. (1996). Granulocyte-Macrophage Colony-stimulating Factor Stimulates JAK2 Signaling Pathway and Rapidly Activates p93[IMAGE], STAT1 p91, and STAT3 p92 in Polymorphonuclear Leukocytes. J. Biol. Chem. 271: 3562-3567 [Abstract] [Full Text]
Tellado, J. M., Christou, N. V. (1993). Circulating and Exudative Polymorphonuclear Neutrophil Priming and Oxidative Capacity in Anergic Surgical Patients. Arch Surg 128: 691-695 [Abstract]
Tellado, J. M., Giannias, B., Kapadia, B., Chartrand, L., de Santis, M., Christou, N. V. (1990). Anergic Patients Before Elective Surgery Have Enhanced Nonspecific Host-Defense Capacity. Arch Surg 125: 49-53 [Abstract]