Neutrophil binding protein

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

L. inocua ferritin site however, is the first described so far that has ligands belonging to two different subunits, and is not contained within a four-helix bundle. Recently it has been suggested that the neutrophil-activating protein of Helicobacter pylori, the major antigen of the immune response in infected individuals, is also a dodecameric ferritin, capable of binding up to 500 iron atoms per oligomer (Tonello et ah, 1999). 

The peroxidase-negative granules produced later in neutrophil development are termed secondary or specific granules (because they stain only with specific dyes). They are twice as abundant in the cytoplasm of the mature neutrophil as the azurophilic granules. Specific granules contain much of the lysozyme, lactoferrin, vitamin-B 12-binding protein, adhesin receptors, fMet-Leu-Phe receptors, and cytochrome b.245. 

Cockcroft, S., Stutchfield, J. (1989). ATP stimulates secretion in human neutrophils and HL60 cells via a pertussis toxin-sensitive guanine nucleotide-binding protein coupled to phospholipase C. FEBS Lett. 245,25-9. 

Actin comprises about 5-8% of the total protein of the neutrophil, and in resting cells about 50-70% of the actin pool exists as a monomer. This proportion of monomeric G-actin is far in excess of what would be predicted from the critical concentration for actin assembly in vitro. Thus, in vivo actin polymerisation and depolymerisation is regulated by the activities of a number of binding proteins, cations and other regulatory molecules, which are in turn regulated by the activation status of the cell. 

Assembly of the actin network merely by interaction with these binding proteins can itself account for pseudopodia formation and propulsive movement. However, there is some evidence to suggest that F-actin-myosin interactions are required for vectorial movement hence it has been demonstrated that pseudopodia contain filament networks comprising actin and myosin. Myosin plays a role in the contractile movement of neutrophils in a... 

Knaus, U. G., Heyworth, P. G., Kinsella, T., Cumutte, J. T., Bokoch, G. M. (1992). Purification and characterisation of Rac2. A cytosolic GTP-binding protein that regulates human neutrophil NADPH oxidase. J. Biol. Chem. 267, 23575-82. 

Almost all receptor-mediated neutrophil functions are mediated via GTP-binding proteins (G-proteins), which provide the link between occupancy of plasma membrane receptors and the activation of intracellular enzymes, such as phospholipases and protein kinases. There are two groups of G-proteins those that are heterotrimeric and those with low molecular weight. 

Figure 6.12. Calciosomes, the intracellular Ca2+ store in neutrophils. Calciosomes are believed to possess three important components (i) the Ins 1,4,5-P3 (IP3) receptor, occupancy of which releases Ca2+ from the calciosome, (ii) a Ca2+-dependent ATPase, responsible for loading the calciosome with cytoplasmic Ca2+ and (iii) calreticulin, a Ca2+-binding protein.

These latter observations suggest a role for arachidonic acid as a genuine second messenger, and further work is necessary to assess if such a role exists during neutrophil activation. It has also been proposed that arachidonic acid may dissociate p21rac and GDI ( 5.3.2.3), thus allowing the small GTP-binding protein to interact with pAl-phox and p66-phox in the assembly of active NADPH oxidase complexes. 

Gabig, T. G., Eklund, E. A., Potter, G. B., Dykes, J. R., II (1990). A neutrophil GTP-binding protein that regulates cellfree NADPH oxidase activation is located in the cytosolic fraction. J. Immunol. 145,945-51. 

Khachatrian, L., Rubins, J. B., Manning, E. C., Dexter, D., Tauber, A. I., Dickey, B. F. (1990). Subcellular distribution and characterization of GTP-binding proteins in human neutrophils. Biochim. Biophys. Acta 1054, 237-45. 

Weingarten, R., Bokoch, G. M. (1990). GTP binding proteins and signal transduction in the human neutrophil. Immunol. Lett. 26, 1-6. 

Teneberg, S., Miller-Podraza, H., Lampert, H. C., Evans, D. J., Jr., Evans, D. G., Danielsson, D., and Karlsson, K. A. (1997). Carbohydrate binding specificity of the neutrophil-activating protein of Helicobacter pylori. ]. Biol. Chem. 272,19067-19071. 

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... 

Neutrophil-Specific Granule Deficiency. In this rare disorder, secondary or specific granules in neutrophils are absent. The defect may arise from a mutation that leads to the loss of function of the transcription factor CCAAT/enhancer binding protein e (C/EBPe), which is needed for neutrophil response to inflammation (91). Specific granule deficiency affecfs fhe migration of neutrophils. 

Lekstrom-Himes, J. A., and Xanfiiopoulos, K. G., CCAAT/enhancer binding protein s is critical for effective neutrophil-mediated response to inflammatory challenge. Blood 93, 3096-3105 (1999). 

A variety of other calcium transport systems are associated with Ca21-activated ATPases. The extraembryonic structure, the chorioallantoic membrane, of the chick embryo is responsible for the translocation of over 120 mg of eggshell calcium into (he embryo during development. The enzyme responsible for this is a (Ca2+, Mg2+)-ATPase with Km values for Ca2+ of 30 p,mol dm-3 and 0.3 mmol dm-3, and a molecular weight of 170 000. The enzyme can be crossiinked and co-isolated with a calcium-binding protein.158 Transport of Ca2+ is also associated with (Ca2+, Mg2+)-ATPases in neutrophil plasma membranes,159 transverse tubule membranes from rabbit skeletal muscle,160 rabbit myocardial membrane,161 endoplasmic reticulum,162 sar-colemma,163 brain microsomes,164 the Golgi apparatus165 and rat liver plasma membranes.166... 

Arcaro, A. 1998. The small GTP-binding protein Rac promotes the dissociation of gelsolin from actin filaments in neutrophils. J Biol Chem. 273 805—13. 

Kerkhoff C, Klempt M, Kaever V, Sorg C. 1999. The two calcium-binding proteins, S100A8 and S100A9, are involved in the metabolism of arachidonic acid in human neutrophils. J Biol Chem 274(46) 32672-32679. 

T4. Thelen, M., Wymann, M. P., and Langen, H., Wortmannin binds specifically to 1-pho-sphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes. Proc. Natl. Acad. Sci. USA 91, 4960-4964 (1994). 

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