Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Chemical Compound Review:

N-Formyl-methionyl-leucyl-phenylalanine 2-[[2-[(2-formamido-4- methylsulfanyl...

Synonyms: AGN-PC-00YI6G, CHEMBL441488, BSPBio_003199, KBioGR_001314, CCG-40032, ...

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of F-Met-leu-phe

We studied the pretreatment of human polymorphonuclear neutrophils (PMN) with purified preparations of the anthrax toxin components--protective antigen (PA), edema factor (EF), and lethal factor (LF)--and their effects on release of superoxide anion (O-2) after stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) [1].
The isolated perfused hearts of rabbits previously subjected to in vivo left ventricular myocardial infarction (LVMI) show a 5-10-fold increase in f-Met-Leu-Phe (FMLP) and bradykinin (BK)-stimulated eicosanoid metabolite production relative to noninfarcted hearts [2].
Thus alanyl-glycyl-seryl-glutamic acid produces colitis independent of proinflammatory eicosanoids while eicosanoid release could contribute to colitis produced by n-formyl-methionyl-leucyl-phenylalanine methyl ester [3].
Priming of human neutrophils with N-formyl-methionyl-leucyl-phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway [4].
In addition to disrupted glucose homeostasis, GSD-Ib patients have unexplained and unexpected defects in neutrophil respiratory burst, chemotaxis and calcium flux, in response to the bacterial peptide f-Met-Leu-Phe, as well as intermittent neutropenia [5].

Psychiatry related information on F-Met-leu-phe

The data show that cord blood neutrophils produce increased amounts of O2- and H2O2 largely because of a prolonged reaction time to fMLP [6].

High impact information on F-Met-leu-phe

This lipid linkage of the receptor on neutrophils suggests that its release may be important for its function, and indeed FcRIII release was observed on stimulation of neutrophils by an inflammatory bacterial peptide (f-Met-Leu-Phe), suggesting a role for FcRIII shedding in inflammatory reactions [7].
In intact cells and in a reconstituted in vitro system, the amount of carboxyl methylation of Ras-related proteins increased in response to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) [8].
Increased neutrophil stiffness, actin assembly, and retention in both 5-micrometer pores and the pulmonary vasculature were seen in response to N-formyl-methionyl-leucyl-phenylalanine [9].
Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine [10].
A latent pool of Mac-1 that can be expressed on granulocyte surfaces in response to secretory stimuli, such as f-Met-Leu-Phe, was also lacking in patients [11].

Chemical compound and disease context of F-Met-leu-phe

Intracolonic administration of n-formyl-methionyl-leucyl-phenylalanine (chemotactic for neutrophils); its methyl ester (chemotactic for monocytes), and alanyl-glycyl-seryl-glutamic acid (chemotactic for eosinophils) all produced colitis (assessed grossly and histologically) within 4 days [3].
When stimulated with the calcium-ionophore A23187, platelet activating factor (PAF) or the microbial agent n-formyl-Methionyl-Leucyl-Phenylalanine (fMLP), significantly increased release of elastase and superoxide anion was noted in both groups with pulmonary hypertension [12].
Neutrophils exposed to Aroclor 1242 or fMLP produced significant O2-. Pretreatment of intact neutrophils with pertussis toxin or cholera toxin or exposure of permeabilized cells to GDPbetaS significantly inhibited O2- production in fMLP-treated neutrophils but did not alter the response to Aroclor 1242 [13].
At concentrations below 10 micrograms/ml, diclofenac in the gel reduced, in a dose-dependent manner, the directed locomotion of PMN induced by a gradient of C5a-activated serum, peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) or Klebsiella pneumoniae culture supernatant (KPCS) [14].
Sulfasalazine, a drug useful in the therapy of inflammatory bowel disease, was found to block N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced arthritis in rabbits as well as FMLP-induced superoxide production and chemotaxis in human neutrophils in vitro [15].

Biological context of F-Met-leu-phe

Significant chemotaxis defects were also seen in response to N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, or macrophage inflammatory protein-2 [16].
The apparent membrane potential changes elicited by f-Met-Leu-Phe and PMA in normal PMN were reduced or entirely absent in PMN obtained from patients with CGD but normal in PMN from other patients [17].
The decreased binding of f-Met-Leu-Phe was not associated with hydrolysis of chemotactic peptide by washed cells, although peptide hydrolysis was caused by cell products secreted extracellularly after vigorous exocytosis [18].
These manipulations also resulted in reversal of ex vivo FMLP-induced coronary vasoconstriction as well as augmentation of BK-induced coronary vasodilation [2].
Intestinal absorption and enterohepatic circulation of N-formyl-methionyl-leucyl-125I-tyrosine, a bioactive synthetic analog of the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine has been investigated in the rat [19].

Anatomical context of F-Met-leu-phe

We found that the chemotactic bacterial peptide, N-formyl- methionyl-leucyl-phenylalanine (fMLP), was able to specifically attenuate Ca2+ mobilization in human phagocytes induced by SAA, but only at very high concentrations, suggesting that SAA uses a low affinity fMLP receptor [20].
All 17 malignant effusions, representing 15 tumor types, inhibited monocyte polarization induced by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine by 45-89% (mean 55.9 +/- 12.7%, P less than 0.01) in blinded assays [21].
The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP, 0.1 microM) enhanced the adherence of neutrophils to endothelial cells twofold (18 +/- 2% vs. 39 +/- 3% adherence, P less than 0.001) and caused substantial neutrophil-mediated injury to endothelial cells (2 +/- 2% vs. 39 +/- 4% cytotoxicity, P less than 0.001) [22].
In the human amnion system, neutrophils were shown to penetrate through the tissue when the peptide chemoattractant f-Met-Leu-Phe was placed on the opposing side [23].
RESULTS: Unactivated eosinophils (i.e., no granulocyte/macrophage colony-stimulating factor [GM-CSF] preexposure) did not migrate across T84 monolayers in the presence of transepithelial gradients of C5a, n-formyl-methionyl-leucyl-phenylalanine (fMLP), or platelet-activating factor (PAF) [24].

Associations of F-Met-leu-phe with other chemical compounds

LPS pretreatment increased superoxide (O2-) generation nearly 10-fold in response to N-formyl methionyl leucyl phenylalanine (fMLP) [25].
In addition, priming of intact neutrophils with low concentrations of the chemoattractant N-formyl-methionyl-leucyl-phenylalanine or the tumor promoter phorbol myristate acetate replaced the soluble factor requirement for NADPH oxidase activation by arachidonate in the high speed pellet [26].
Pretreatment of the HUVEC with anti-ICAM-1 MAbs produced greater than 50% inhibition of attachment to HUVEC, and IL-1 (0.5 U/ml)- or lipopolysaccharide (LPS) (10 ng/ml)-stimulated HUVEC, and greater than 99% inhibition of f-Met-Leu-Phe (0.5 nM) enhanced adherence [27].
The objective of this study was to determine the effects of luminal perfusion with N-formyl methionyl-leucyl-phenylalanine (FMLP), a bacterial product that attracts and activates granulocytes, on mucosal permeability in different regions of the rat small intestine and colon [28].
However, addition of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) which does not stimulate proliferation in macrophages caused a marked and rapid increase in the levels of Ins(1,4,5)P3, inositol bisphosphate and inositol monophosphate, and a decrease in the amount of PtdIns(4,5)P2 [29].

Gene context of F-Met-leu-phe

These characteristics and the time-courses of the responses stimulated by IL-8 were similar to those stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP), except that the cells stimulated by IL-8 showed shorter duration and less magnitude in some responses [30].
LSP1(-) neutrophils demonstrate an enhanced chemotactic response in vitro to N-formyl methionyl-leucyl-phenylalanine (FMLP) and to the C-X-C chemokine, KC, indicating that their enhanced influx into the peritoneum may be a result of increased motility [31].
The chemotactic peptide f-Met-Leu-Phe (fMLP) stimulates leukocyte functions through binding and activation of a specific G-protein-coupled formyl peptide receptor (FPR) [32].
We earlier demonstrated that tumor necrosis factor-alpha (TNF-alpha) as well as N-formyl-methionyl-leucyl-phenylalanine treatment leads to increased phosphorylation and activation of p38 kinase in human neutrophils [33].
Moreover, stimulation with f-met-leu-phe resulted in an enhanced response after preincubation with TNF or LT [34].

Analytical, diagnostic and therapeutic context of F-Met-leu-phe

At optimum concentrations, f-Met-Leu-Phe elicited rates of superoxide formation that could not be exceeded under other stimulatory conditions including PMA after treatment with IFN gamma [35].
Human neutrophils (5 X 10(6) cells/ml) were placed in the upper compartment of a combined chemotaxis/resistance chamber and stimulated for 40 min by a gradient of 10(-7) M n-formyl-methionyl-leucyl-phenylalanine to traverse a confluent monolayer of canine kidney epithelial cells grown on micropore filters [36].
Autoradiography of 125I-labeled C5a or f-Met-Leu-Phe analogue showed specific binding of the peptides to cells dispersed in the vessel wall, but more frequently at the periphery [37].
Whereas intravenous injections of endotoxin also caused modest inhibition of the vascular permeability changes induced in rabbit skin by the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), exudation of polymorphonuclear leukocytes was unaffected [38].
We have used a new centrifugation assay to examine the effects of highly purified human C5a and C5a des Arg, as well as effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP), on both the extent and strength of human polymorphonuclear leukocyte (PMN) adherence to monolayers of cultured human umbilical vein endothelial cells [39].

References

Anthrax toxin blocks priming of neutrophils by lipopolysaccharide and by muramyl dipeptide. Wright, G.G., Mandell, G.L. J. Exp. Med. (1986) [Pubmed]
Role of invading leukocytes in enhanced atrial eicosanoid production following rabbit left ventricular myocardial infarction. Freed, M.S., Needleman, P., Dunkel, C.G., Saffitz, J.E., Evers, A.S. J. Clin. Invest. (1989) [Pubmed]
Chemotactic peptide-induced acute colitis in rabbits. LeDuc, L.E., Nast, C.C. Gastroenterology (1990) [Pubmed]
Priming of human neutrophils with N-formyl-methionyl-leucyl-phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway. Karnad, A.B., Hartshorn, K.L., Wright, J., Myers, J.B., Schwartz, J.H., Tauber, A.I. Blood (1989) [Pubmed]
Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter. Chen, L.Y., Shieh, J.J., Lin, B., Pan, C.J., Gao, J.L., Murphy, P.M., Roe, T.F., Moses, S., Ward, J.M., Lee, E.J., Westphal, H., Mansfield, B.C., Chou, J.Y. Hum. Mol. Genet. (2003) [Pubmed]
Effect of low neutral endopeptidase expression on response to fMLP. Kaplan, S.S., Park, J., Basford, R.E., Zdziarski, U.E., Penchansky, L. J. Lab. Clin. Med. (1992) [Pubmed]
The PI-linked receptor FcRIII is released on stimulation of neutrophils. Huizinga, T.W., van der Schoot, C.E., Jost, C., Klaassen, R., Kleijer, M., von dem Borne, A.E., Roos, D., Tetteroo, P.A. Nature (1988) [Pubmed]
Carboxyl methylation of Ras-related proteins during signal transduction in neutrophils. Philips, M.R., Pillinger, M.H., Staud, R., Volker, C., Rosenfeld, M.G., Weissmann, G., Stock, J.B. Science (1993) [Pubmed]
Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries. Worthen, G.S., Schwab, B., Elson, E.L., Downey, G.P. Science (1989) [Pubmed]
Spontaneous skin ulceration and defective T cell function in CD18 null mice. Scharffetter-Kochanek, K., Lu, H., Norman, K., van Nood, N., Munoz, F., Grabbe, S., McArthur, M., Lorenzo, I., Kaplan, S., Ley, K., Smith, C.W., Montgomery, C.A., Rich, S., Beaudet, A.L. J. Exp. Med. (1998) [Pubmed]
Inherited deficiency of the Mac-1, LFA-1, p150,95 glycoprotein family and its molecular basis. Springer, T.A., Thompson, W.S., Miller, L.J., Schmalstieg, F.C., Anderson, D.C. J. Exp. Med. (1984) [Pubmed]
Increased neutrophil mediator release in patients with pulmonary hypertension--suppression by inhaled iloprost. Rose, F., Hattar, K., Gakisch, S., Grimminger, F., Olschewski, H., Seeger, W., Tschuschner, A., Schermuly, R.T., Weissmann, N., Hanze, J., Sibelius, U., Ghofrani, H.A. Thromb. Haemost. (2003) [Pubmed]
Protein tyrosine kinase involvement in the production of superoxide anion by neutrophils exposed to Aroclor 1242, a mixture of polychlorinated biphenyls. Tithof, P.K., Watts, S., Ganey, P.E. Biochem. Pharmacol. (1997) [Pubmed]
Diclofenac sodium, a negative chemokinetic factor for neutrophil locomotion. Perianin, A., Gougerot-Pocidalo, M.A., Giroud, J.P., Hakim, J. Biochem. Pharmacol. (1985) [Pubmed]
Sulfasalazine inhibition of binding of N-formyl-methionyl-leucyl-phenylalanine (FMLP) to its receptor on human neutrophils. Stenson, W.F., Mehta, J., Spilberg, I. Biochem. Pharmacol. (1984) [Pubmed]
A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation. Betsuyaku, T., Liu, F., Senior, R.M., Haug, J.S., Brown, E.J., Jones, S.L., Matsushima, K., Link, D.C. J. Clin. Invest. (1999) [Pubmed]
Use of lipophilic probes of membrane potential to assess human neutrophil activation. Abnormality in chronic granulomatous disease. Seligmann, B.E., Gallin, J.I. J. Clin. Invest. (1980) [Pubmed]
Role of secretory events in modulating human neutrophil chemotaxis. Gallin, J.I., Wright, D.G., Schiffmann, E. J. Clin. Invest. (1978) [Pubmed]
Bacterial chemotactic oligopeptides and the intestinal mucosal barrier. Ferry, D.M., Butt, T.J., Broom, M.F., Hunter, J., Chadwick, V.S. Gastroenterology (1989) [Pubmed]
A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells. Su, S.B., Gong, W., Gao, J.L., Shen, W., Murphy, P.M., Oppenheim, J.J., Wang, J.M. J. Exp. Med. (1999) [Pubmed]
Inhibitors of monocyte responses to chemotaxins are present in human cancerous effusions and react with monoclonal antibodies to the P15(E) structural protein of retroviruses. Cianciolo, G., Hunter, J., Silva, J., Haskill, J.S., Snyderman, R. J. Clin. Invest. (1981) [Pubmed]
Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells. Cronstein, B.N., Levin, R.I., Belanoff, J., Weissmann, G., Hirschhorn, R. J. Clin. Invest. (1986) [Pubmed]
Laminin promotes rabbit neutrophil motility and attachment. Terranova, V.P., DiFlorio, R., Hujanen, E.S., Lyall, R.M., Liotta, L.A., Thorgeirsson, U., Siegal, G.P., Schiffmann, E. J. Clin. Invest. (1986) [Pubmed]
Human eosinophils migrate across an intestinal epithelium in response to platelet-activating factor. Resnick, M.B., Colgan, S.P., Parkos, C.A., Delp-Archer, C., McGuirk, D., Weller, P.F., Madara, J.L. Gastroenterology (1995) [Pubmed]
Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly. DeLeo, F.R., Renee, J., McCormick, S., Nakamura, M., Apicella, M., Weiss, J.P., Nauseef, W.M. J. Clin. Invest. (1998) [Pubmed]
Activation of the respiratory burst enzyme from human neutrophils in a cell-free system. Evidence for a soluble cofactor. McPhail, L.C., Shirley, P.S., Clayton, C.C., Snyderman, R. J. Clin. Invest. (1985) [Pubmed]
Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. Smith, C.W., Rothlein, R., Hughes, B.J., Mariscalco, M.M., Rudloff, H.E., Schmalstieg, F.C., Anderson, D.C. J. Clin. Invest. (1988) [Pubmed]
The chemotactic peptide N-formyl methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat. von Ritter, C., Sekizuka, E., Grisham, M.B., Granger, D.N. Gastroenterology (1988) [Pubmed]
The haemopoietic growth factors interleukin 3 and colony stimulating factor-1 stimulate proliferation but do not induce inositol lipid breakdown in murine bone-marrow-derived macrophages. Whetton, A.D., Monk, P.N., Consalvey, S.D., Downes, C.P. EMBO J. (1986) [Pubmed]
Stimulation and priming of human neutrophils by interleukin-8: cooperation with tumor necrosis factor and colony-stimulating factors. Yuo, A., Kitagawa, S., Kasahara, T., Matsushima, K., Saito, M., Takaku, F. Blood (1991) [Pubmed]
LSP1 modulates leukocyte populations in resting and inflamed peritoneum. Jongstra-Bilen, J., Misener, V.L., Wang, C., Ginzberg, H., Auerbach, A., Joyner, A.L., Downey, G.P., Jongstra, J. Blood (2000) [Pubmed]
Activation of the mitogen-activated protein kinase pathway by fMet-leu-Phe in the absence of Lyn and tyrosine phosphorylation of SHC in transfected cells. Torres, M., Ye, R.D. J. Biol. Chem. (1996) [Pubmed]
Acetyl-CoA:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase is directly activated by p38 kinase. Nixon, A.B., O'Flaherty, J.T., Salyer, J.K., Wykle, R.L. J. Biol. Chem. (1999) [Pubmed]
Human tumor necrosis factor is a potent activator of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: comparison with human lymphotoxin. Kapp, A., Zeck-Kapp, G., Blohm, D. J. Invest. Dermatol. (1989) [Pubmed]
Activation of monocytes by interferon-gamma has no effect on the level or affinity of the nicotinamide adenine dinucleotide-phosphate oxidase and on agonist-dependent superoxide formation. Thelen, M., Wolf, M., Baggiolini, M. J. Clin. Invest. (1988) [Pubmed]
The effect of neutrophil migration on epithelial permeability. Milks, L.C., Conyers, G.P., Cramer, E.B. J. Cell Biol. (1986) [Pubmed]
Contractile effect of the chemotactic factors f-Met-Leu-Phe and C5a on the human isolated umbilical artery. Role of cyclooxygenase products and tissue macrophages. Marceau, F., deBlois, D., Laplante, C., Petitclerc, E., Pelletier, G., Grose, J.H., Hugli, T.E. Circ. Res. (1990) [Pubmed]
Antiinflammatory effects of endotoxin. Inhibition of rabbit polymorphonuclear leukocyte responses to complement (C5)-derived peptides in vivo and in vitro. Rosenbaum, J.T., Hartiala, K.T., Webster, R.O., Howes, E.L., Goldstein, I.M. Am. J. Pathol. (1983) [Pubmed]
Chemotactic peptides modulate adherence of human polymorphonuclear leukocytes to monolayers of cultured endothelial cells. Charo, I.F., Yuen, C., Perez, H.D., Goldstein, I.M. J. Immunol. (1986) [Pubmed]

Contributions to this collaborative article are from individual authors of WikiGenes or mined by the WikiGenes Data Mining Engine from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.