Does Formyl-Methionyl-Leucyl-Phenylalanine Exert a Physiological Role in Labor in Women?1

Buzzi, Marco; Vesce, Fortunato; Ferretti, Maria Enrica; Fabbri, Elena; Biondi, Carla

doi:10.1095/biolreprod60.5.1211

Cited by 11 publications

(3 citation statements)

References 24 publications

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“…Compared with these molecules, the affinity and potency of CHIPS to bind and block the FPR is at least 1000-fold higher (32). The unique properties of CHIPS to specifically inhibit the FPR with high affinity could be an important new tool to further stimulate the fundamental research on the mechanisms underlying the FPR and its role in disease processes (16,17,32,33).…”

Section: Discussionmentioning

confidence: 99%

N-Terminal Residues of the Chemotaxis Inhibitory Protein of Staphylococcus aureus Are Essential for Blocking Formylated Peptide Receptor but Not C5a Receptor

Haas

Kleibeuker

et al. 2004

The Journal of Immunology

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Staphylococcus aureus excretes a factor that specifically and simultaneously acts on the C5aR and the formylated peptide receptor (FPR). This chemotaxis inhibitory protein of S. aureus (CHIPS) blocks C5a- and fMLP-induced phagocyte activation and chemotaxis. Monoclonal anti-CHIPS Abs inhibit CHIPS activity against one receptor completely without affecting the other receptor, indicating that two distinct sites are responsible for both actions. A CHIPS-derived N-terminal 6 aa peptide is capable of mimicking the anti-FPR properties of CHIPS but has no effect on the C5aR. Synthetic peptides in which the first 6 aa are substituted individually for all other naturally occurring amino acids show that the first and third residue play an important role in blocking the FPR. Using an Escherichia coli expression system, we created mutant CHIPS proteins in which these amino acids are substituted. These mutant proteins have impaired or absent FPR- but still an intact C5aR-blocking activity, indicating that the loss of the FPR-blocking activity is not caused by any structural impairment. This identifies the first and third amino acid, both a phenylalanine, to be essential for CHIPS blocking the fMLP-induced activation of phagocytes. The unique properties of CHIPS to specifically inhibit the FPR with high affinity (kd = 35.4 ± 7.7 nM) could be an important new tool to further stimulate the fundamental research on the mechanisms underlying the FPR and its role in disease processes.

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Section: Discussionmentioning

confidence: 99%

N-Terminal Residues of the Chemotaxis Inhibitory Protein of Staphylococcus aureus Are Essential for Blocking Formylated Peptide Receptor but Not C5a Receptor

Haas

Kleibeuker

et al. 2004

The Journal of Immunology

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“…However, in the mid-1990s, the presence of FPR has been demonstrated in different nonhematopoietic cells, such as hepatocytes, dendritic cells and astrocytes, suggesting that formylpeptides may influence cellular mechanisms that are independent of the inflammatory response [22,23]. For this purpose, Buzzi, Vesce, Ferretti, Fabbri and Biondi [24] demonstrated the presence of specific binding sites for [ 3 H]fMLP in human amniotic membranes and that their expression is different in membranes obtained from laboring and nonlaboring women. In particular, high and low affinity binding have been identified in the former, while only low affinity receptors were found in the latter.…”

Section: Formylpeptide Receptormentioning

confidence: 99%

Studies on Human Neutrophil Biological Functions by Means of Formylpeptide Receptor Agonists and Antagonists

Dalpiaz

Spisani

Biondi

et al. 2003

CDTIEMD

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Phagocytes are activated by several extracellular signals, including formyl-peptides derived from bacterial proteins or disrupted cells. The most intensely studied member of the formylpeptide family is the synthetic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), whose specific receptors have been identified on neutrophil plasma membrane and subsequently cloned. The fMLP-receptor interaction activates multiple transduction pathways responsible for various neutrophil functions such as adhesion, chemotaxis, exocytosis of secretory granules and superoxide anion production, which represent the physiological response to bacterial infection and tissue damage. An unresolved question is whether signaling requirements are identical or specific for each physiological function. The development of fMLP receptor agonists and antagonists has led to an improvement of our knowledge about the above issue. Of particular interest is the possibility that receptorial antagonists, able to transiently inhibit neutrophil responses to formylpeptides, could be therapeutic agents in the treatment of inflammation-related diseases. Aim of this review is, i) to summarise the current understanding of the series of events that begins at the level of formylpeptide-receptor interaction and is responsible for the activation of transduction pathways, which finally determine neutrophil response; ii) to define the state of art regarding the synthesis as well as the biological actions of fMLP receptor agonists and antagonists.

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“…As regards the modulation of the inflammatory response, it must be considered that the mediators of cellular inflammation are also involved in the main physiological events of fertility, such as menstruation and delivery ( 32 ) Accordingly, the levels of the receptor ligands for the inflammatory peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) in amniotic fluid are stable during gestation, while they are significantly increased by labour, along with the expression of fMLP receptor in amnion tissue. These findings indicate that fMLP system modulates the events of physiological labour ( 33 – 35 ).…”

Section: The Need To Distinguish Humoral From Cellular Gestational Im...mentioning

confidence: 65%

The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia

Vesce

Battisti²,

Crudo³

2022

Front. Immunol.

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Pregnancy can be defined a vascular event upon endocrine control. In the human hemo-chorial placentation the chorionic villi penetrate the wall of the uterine spiral arteries, to provide increasing amounts of nutrients and oxygen for optimal fetal growth. In any physiological pregnancy the natural maternal response is of a Th1 inflammatory type, aimed at avoiding blood loss through the arteriolar wall openings. The control of the vascular function, during gestation as in any other condition, is achieved through the action of two main types of prostanoids: prostaglandin E2 and thromboxane on the one hand (for vasoconstriction and coagulation), prostacyclin on the other (for vasodilation and blood fluidification). The control of the maternal immune response is upon the responsibility of the fetus itself. Indeed, the chorionic villi are able to counteract the natural maternal response, thus changing the inflammatory Th1 type into the anti-inflammatory Th2. Clinical and experimental research in the past half century address to inflammation as the leading cause of abortion, pregnancy loss, premature delivery and related pulmonary, cerebral, intestinal fetal syndromes. Increased level of Interleukin 6, Interleukin 1-beta, Tumor Necrosis Factor-alfa, Interferon-gamma, are some among the well-known markers of gestational inflammation. On the other side, COVID-19 pneumonia is a result of extensive inflammation induced by viral replication within the cells of the respiratory tract. As it may happen in the uterine arteries in the absence of an effective fetal control, viral pneumonia triggers pulmonary vascular coagulation. The cytokines involved in the process are the same as those in gestational inflammation. As the fetus breathes throughout the placenta, fetal death from placental thrombosis is similar to adult death from pulmonary thrombosis. Preventing and counteracting inflammation is mandatory in both conditions. The most relevant literature dealing with the above-mentioned concepts is reviewed in the present article.

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Does Formyl-Methionyl-Leucyl-Phenylalanine Exert a Physiological Role in Labor in Women?1

Cited by 11 publications

References 24 publications

N-Terminal Residues of the Chemotaxis Inhibitory Protein of Staphylococcus aureus Are Essential for Blocking Formylated Peptide Receptor but Not C5a Receptor

N-Terminal Residues of the Chemotaxis Inhibitory Protein of Staphylococcus aureus Are Essential for Blocking Formylated Peptide Receptor but Not C5a Receptor

Studies on Human Neutrophil Biological Functions by Means of Formylpeptide Receptor Agonists and Antagonists

The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia

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