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fMLP Pathway

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Neutrophils play an important role in the host defense by invading microbial pathogens. Upon infection neutrophils become activated through interaction with chemo attractants and cytokines. These ligands bind to a variety of cell surface receptors, including heterotrimeric GPCR (G-Protein Coupled Receptors) for fMLP (N-formyl-Met-Leu-Phe) and PAF (Platelet Activating Factor), and tyrosine kinase-associated receptors for GMCSF (Granulocyte-Macrophage Colony Stimulating Factor). Receptor activation triggers intracellular signal transduction pathways, resulting in the correct biological response, for instance, migration, phagocytosis, antibody-dependent cell mediated cytotoxicity, degranulation, superoxide production, transcriptional activation, and actin reorganization. If G-protein is blocked by pertussis toxin, cells do not respond to fMLP (Ref.1). Improper functioning of neutrophils is implicated in the pathogenesis of a variety of inflammatory diseases resulting in tissue damage (Ref.2). [...]


1.Recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) regulates f Met-Leu-Phe receptors on human neutrophils.
Atkinson YH, Lopez AF, Marasco WA, Lucas CM, Wong GG, Burns GF, Vadas MA.
Immunology. 1988 Jul; 64(3): 519-25.
2.Differential fMet-Leu-Phe- and platelet-activating factor-induced signaling toward Ral activation in primary human neutrophils.
M'Rabet L, Coffer PJ, Wolthuis RM, Zwartkruis F, Koenderman L, Bos JL.
J Biol Chem. 1999 Jul 30; 274(31): 21847-52.
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