Disease relevance of Formyl met leu phe

• We related these events to in vivo FMLP-induced neutropenia [1].
• However, the oxidative burst stimulated by S. aureus and formyl-Met-Leu-Phe, but not phorbol myristate acetate, was significantly enhanced in PMN from patients with chronic renal insufficiency [2].
• Newcastle disease virus neuraminidase primes neutrophils for stimulation by galectin-3 and formyl-Met-Leu-Phe [3].
• In contrast, in granulocytes from hypercholesterolemic patients, formyl-Met-Leu-Phe triggered an intensive pertussis toxin-insensitive oxidative burst and leukotriene synthesis [4].
• High-speed supernatant fluids derived from sonicated Coxiella burnetii contained considerable acid phosphatase activity when assayed by using 4-methylumbelliferylphosphate; they also contained a factor that blocked superoxide anion production by human neutrophils stimulated with formyl-Met-Leu-Phe [5].

High impact information on Formyl met leu phe

• A similar conclusion has been applied to explain the actions of formyl-Met-Leu-Phe on neutrophils, and it may be that receptors that couple through intrinsic tyrosine kinases or through G proteins stimulate the same step in 3-phosphorylated inositol lipid metabolism [6].
• The loss of IL-1 binding capacity caused by FMLP was determined by a reduction in receptor number with no change in their affinity [7].
• N-t-Boc-Met-Leu-Phe, an antagonist for the FMLP receptor, inhibited the loss of IL-1 binding capacity induced by FMLP [7].
• In response to formyl-Met-Leu-Phe (fMLP) receptor stimulation, beta-arrestin Ral-GDS protein complexes dissociate and Ral-GDS translocates with beta-arrestin from the cytosol to the plasma membrane, resulting in the Ras-independent activation of the Ral effector pathway required for cytoskeletal rearrangement [8].
• The analysis of biological effects of TPO on PMN demonstrated that TPO, at concentrations of 1-10 ng/ml, primes the response of PMN to n-formyl-met-leu-phe (FMLP) by inducing an early oxidative burst [9].

Chemical compound and disease context of Formyl met leu phe

• To examine the contribution of cell adhesion molecules in this process, we used blocking monoclonal antibodies (mAbs) to rat selectins and integrins in a model of PMNL margination (reflected by acute blood neutropenia) induced by N-formyl-met-leu-phe (FMLP) chemotactic factor infusion in normal or lipopolysaccharide (LPS)-primed rats [10].
• The fMLP-induced translocation was blocked by an inhibitor of PI 3-kinase, LY294002, and pertussis toxin [11].
• The activation of the respiratory burst by complement factor 5a (C5a), platelet-activating factor (PAF), formyl-Met-Leu-Phe (fMLP) and neutrophil-activating peptide IL-8 was explored in eosinophils from patients with the hypereosinophilic syndrome [12].
• Chemotactins employed included the complement-derived C3 and C5 fragments, the bacterial chemotactic factor from culture supernatant fluids of Escherichia coli, and the synthetic chemotactic factors Met-Leu-Phe and formyl-Met-Leu-Phe [13].
• Culture medium conditioned by human mononuclear leukocytes (MNL) stimulated with formalin fixed heat-killed Staphylococcus aureus induces a small respiratory burst in human neutrophils, and dramatically increases the response of neutrophils to stimuli such as N-formyl-L-methionyl-L-leucyl-L-phenylalanine [14].

Biological context of Formyl met leu phe

• Dose-response analysis revealed that maximal reduction of IL-1 binding was reached at FMLP concentrations that were also optimal for chemotaxis (50% effective dose = 5 x 10(-9) M) [7].
• In studies of Ab 1-15 effects on membrane-related second messenger pathways, Ab 1-15 augmented both FMLP- and isoproterenol-induced intracellular cAMP accumulation, whereas alpha-chymotrypsin decreased PMN cAMP response to these stimuli [15].
• We studied the time course of change in F-actin content, F-actin distribution, and cell shape after fMLP stimulation [16].
• Out of a large panel of naturally occurring humoral factors tested, only GM-CSF itself, tumor necrosis factor, and formyl-Met-Leu-Phe were found to down-regulate neutrophil GM-CSF receptor expression after a 2-hr exposure at biologically active concentrations (95% +/- 1%, 34% +/- 5%, 48% +/- 8% receptor down-regulation, respectively) [17].
• High and intermediate doses of FMLP caused a dramatic but transient decrease in blood pressure and an increase in respiratory rate [1].

Anatomical context of Formyl met leu phe

• Prior to FMLP infusion, plasma lactoferrin level was 6.4 +/- 4.1 micrograms/ml, and the absolute granulocyte account (AGC) was 2008 +/- 1229 (mean +/- SD) [1].
• Ab 1-14 reduced PMN chemotaxis in response to FMLP by 37% (P less than .02), and unlike Ab 1-15, Ab 1-14 significantly reduced unstimulated PMN binding of complement-coated sheep red blood cells [18].
• Maturation of human myeloid cells is associated with quantitative and qualitative changes in protein kinase C (PKC) and increases in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptors, actin, and actin regulatory proteins [19].
• In contrast, using Syk-deficient primary cells, we show here that Syk does not play a major functional role in chemoattractant/chemokine signaling in neutrophils and mast cells. syk(-/-) neutrophils showed normal respiratory burst and degranulation in response to the bacterial peptide formyl-Met-Leu-Phe (fMLP) [20].
• The 50% effective doses (ED50) for chemotactic responses to C5a, FMLP, or AGSG by neutrophils and eosinophils were 0.05 microgram/ml and 1.0 microgram/ml, 10(-12) M and 10(-10) M, and 10(-7) M and 10(-7) M, respectively [21].

Associations of Formyl met leu phe with other chemical compounds

• Although the initial acidification following fMLP was abrogated by 2-deoxy-D-glucose in both GM-CSFrh-pretreated and GM-CSFrh-untreated granulocytes, retardation of the subsequent phase of alkalinization was observed in GM-CSFrh-primed cells even after inhibition of both glycolytic and mitochondrial metabolism [22].
• These results suggest that PLD plays an important role in fMLP stimulation of both N-acetyl-beta-glucosaminidase release and O2- generation in the primed neutrophils, but that a PLD-independent pathway plays the primary role in O2- generation by the nonprimed neutrophils [23].
• Selective Localization of Recognition Complexes for Leukotriene B4 and Formyl-Met-Leu-Phe within Lipid Raft Microdomains of Human Polymorphonuclear Neutrophils [24].
• A similar pretreatment with PT inhibited thrombin-induced histamine release from BMMC and N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced histamine release from human basophils in a similar dose-dependent fashion [25].
• By use of a recently described and specific inhibitor of cytosolic PLA(2)-alpha (group IV PLA(2)alpha), we show that this enzyme produces virtually all of the arachidonic acid used for the biosynthesis of leukotriene B(4) in fMLP- and opsonized zymosan-stimulated neutrophils, the major eicosanoid produced by these pro-inflammatory cells [26].

Gene context of Formyl met leu phe

• In addition, formyl-Met-Leu-Phe (a FPR ligand), Trp-Lys-Tyr-Met-Val-Met, Hp(2-20) peptide, and F2L (three FPRL2 ligands) inhibited LPS-induced IL-12 production in DCs [27].
• Preincubation with IL-8, MGSA, or ENA-78 enhanced the ability of neutrophils to generate O-2 following stimulation with the bacterial peptide formyl-Met-Leu-Phe [28].
• In formyl-Met-Leu-Phe-stimulated cells, PLD activity as assessed by phosphatidylethanol formation was also associated with both the plasma membrane and endomembranes [29].
• This is in contrast to other neutrophil agonists such as fMLP, interleukin (IL)-8, or GM-CSF, which stimulate multiple MAPK pathways [30].
• Ligation of CGM6 or NCA90 alone did not cause activation of the neutrophil in any of the assays used and did not cause priming of fMLP-induced oxidant production even when a secondary cross-linking reagent was used [31].

Analytical, diagnostic and therapeutic context of Formyl met leu phe

• Intradermal injection of N-formyl-met-leu-phe (FMLP), a potent macrophage chemotactic peptide, induced a macrophage-rich infiltrate at the site of injection [32].
• Guinea pig alveolar macrophages obtained by bronchoalveolar lavage were isolated by adherence for 2 h and stimulated with 1 microM of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) for different time intervals [33].
• Studies of peripheral PMN and monocyte function in CAPD patients have shown that, similar to HD patients, they also have decreased C5a receptors and decreased oxidative metabolic responses to the chemotactic factors C5a and fMLP [34].
• Peripheral blood eosinophils were isolated from 18 human volunteers by negative immunoselection, and secretion of EPO was elicited with 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml cytochalasin B (CytB) in aliquots of 10(5) cells [35].
• Although RNA to TNF-alpha was detected in milk leukocytes by Northern blotting, little TNF-alpha was found in those cells before or after stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine or 4 beta-phorbol-12 beta-myristate-13 alpha-acetate [36].

References