Peptide chemotactic

Previous studies indicate that osmotic gradients promote membrane fusion, while hyperosmotic conditions inhibit membrane fusion during exocytosis. Consistent with this idea is the observation that the release of lysosomal enzymes from rabbit neutrophils, induced by the chemotactic peptide J -formylmethionyl-leucyl-phenylalanine (FMLP), is inhibited almost 80% in a 700-mosmol/kg medium. Inhibition is immediate (within 10 s), increases with osmolality, and is independent of the osmoticant. Neutrophils loaded with the calcium indicator indo-1 exhibit an FMLP-induced calcium signal that is inhibited by hyperosmolality. Hyperosmolality (700 mosmol/kg) increases basal calcium levels and reduces the peak of the calcium signal elicited by FMLP at concentrations ranging from 10 ° to 10 M. 

Neutrophils represent an ideal system for studying osmotic effects on exocytosis. Stimulation of cytochalasin-B-treated neutrophils with the chemotactic peptide Jlf-formylmethionyl-leucyl-phenyl-alanine (FMLP) results in a rapid compound exocytosis up to 80% of lysosomal enzymes are released within 30 s (9-14). Secretion appears to be triggered by a rise in the level of cytosolic free calcium (15-18) promoted in part by entry of extracellular calcium through receptor-gated channels and in part by release of calcium that is sequestered or bound at some intracellular site (19-21). In this presentation, we augment our previously published data (22,23), which demonstrates that lysosomal enzyme release from neutrophils is inhibited under hyperosmotic conditions and that the rise in cytosolic calcium preceding secretion is inhibited as well. 

NADPH oxidase is inactive in resting phagocytic cells and is activated upon contact with various ligands (complement fragment C5a, chemotactic peptides, etc)... 

LeDuc, L.E. and Nast, C.C. (1990). Chemotactic peptide-induced acute colitis in rabbits. Gastroenterology 98, 929-935. 

The differentiation effect of lycopene was associated with elevated expression of several differentiation-related proteins, such as cell surface antigen (CD14), oxygen burst oxidase and chemotactic peptide receptors (Amir et al., 1999). Recently, it has also been reported that lycopene was also able to stimulate the differentiation marker alkaline phosphatase activity in... 

Schmidt, H. H. H. W., Seifert, R., Bohme, E. (1989). Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by a chemotactic peptide, platelet activating factor and leukotriene B4. FEBS Lett. 244, 357-60. 

Billah, M. M., Eckel, S., Mullmann, T. J., Egan, R. W., Siegel, M. I. (1989). Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phosphatidate phosphohydrolase in signal transduction. J. Biol. Chem. 264, 17069-77. 

Zymosan-induced leukotriene B4 generation by human neutrophils is augmented by ihTNF-abut not chemotactic peptide. Immunol. 70,75-81. 

In polymorphonuclear leucocytes (PMNL, neutrophils), secretory responses measured as vitamin B -binding protein release were inhibited by feverfew extract when the response was induced by the chemotactic peptide FMLP or arachidonic acid but not when the calcium ionophore A23187 was... 

Howard, T. H. and Oresajo, C. O. (1985) The kinetics of chemotactic peptide-induced changes in F-actin content, F-actin distribution, and the shape of neutrophil. J. Cell Biol. 101,1078-1085. 

Howard, T. H. and Wang, D. (1987) Calcium ionophore, phorbol ester and chemotactic peptide-induced cytoskeleton reorganization in human neutrophils. J. Clin. Invest. 79,1359-1364. 

Okada, T. Sakuma, L. Fukui, Y Hazeki, O. Ui, M. Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase. J. Biol. Chem., 269, 3563-3567 (1994)... 

Turner, S.J. Domin, J. Waterfield, M.D. Ward, S.G. Westwick, J. The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/ pllO phosphatidylinositol 3-kinase and the class II PI3K-C2a. J. Biol. Chem., 273, 25987-25995 (1998)... 

The chemotactic peptides are also active in the stimulation of release of O and in the release of lysosomal contents Directed locomotion by PMNs is stimulated by a family of tri-, tetra-, and dipeptides which have in common formylated methionine as the first amino acid. Since formylated methionine is the initiator to which other amino acids are added in the synthesis of bacterial protein, small peptides which commence with formylated methionine are likely to be liberated proteolytically at sites of bacterial infection, possibly explaining their great potency as chematoxins. Using superoxide-dependent chemiluminescence (see below) as a measure of synthesis of O , Hatch et al. showed a hierarchy of potency of FMLP > FMP > FMV > FMA. Becker et al. measured the formation of O in suspensions of rabbit PMNs and found that the hierarchy of potency was the same for stimulation of the formation of O7 as it was for stimulation of release of lysosomal enzymes, namely... 

Sklar, L. A., Oades, Z. G., Jesaitis, J., Painter, R. G., and Cochrane, C. G. (1981). Fluoresceinated chemotactic peptide and high-affinity antifluorescein antibody as a probe of the temporal characteristics of neutrophil stimulation. Proc. Natl. Acad. Sci. USA 78, 7540-7544. 

Cytokines IL-6, a2-macroglobulin, macrophage-colony stimulating factor (M-CSF), monocyte chemotactic peptide-1 (MCP-1), platelet activating factor (PAF)... 

Once deposited, there are multiple mechanisms by which an immune complex initiates an inflammatory reaction (Fig. 2). Foremost among these is activation of the complement system. Immune complexes can activate the classical complement pathway as well as, indirectly or directly, the alternative complement pathway. The biologic activities of complement activation which are relevant to tissue inflammation include the generation of anaphylatoxins C5a and C3a (H29) and chemotactic peptide C5a (H29, T6), direct and indirect membrane lysis by the terminal complement components C56789 (T17), leukocytosis by C3e (G8), macrophage activation by Bb (G12), immune complex solubilization by C3b (C21), and immune adherence, the binding and activation of cells bearing complement receptors. 

Parenchymal liver cells Kupffer cells Liver endothelial cells Leucocytes Galactose, polymeric IgA, cholesterol ester-VLDL, LDL Mannose-fucose, galactose (particles), (oxidized) LDL Mannose, acetylated LDL Chemotactic peptide, complement C3b... 

Wallace, P. J., Wersto, R. P., Packman, C. H., andLichtman, M. A. (1984) Chemotactic peptide-induced changes in neutrophil actin conformation. J. Cell. Biol. 99, 1060-1065. 

Colditz, I., Zwahlen, R., Dewald, B., and Baggiolini, M. (1989) In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am. J. Pathol. 134, 755-760. 

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