Neutrophils chemoattraction

C5-derived peptide in serum. This molecule lacks anaphylatoxin activity (i.e. it cannot cause smooth muscle contraction), and its ability to cause che-motaxis in neutrophils is about 10-20 times lower than that of C5a. However, human serum also contains a heat-stable, anionic protein termed co-chemotaxin (relative molecular mass = 60 kDa), which acts in a concentration-dependent manner to permit C5a des Arg to act as a chemoattractant for neutrophils. Thus, C5a des Arg plus cochemotaxin working together probably account for most of the neutrophil chemoattractant activity in vivo following complement activation. The mechanism of action of cochemotaxin is unknown, but it may form a physical complex by attaching to a sialic acid residue on the oligosaccharide chain of C5a des Arg. Deglycosylation of C5a des Arg increases its chemoattractant activity more than 10-fold, and its dependency upon cochemotaxin is decreased. 

Incubation times of 0.5-1 h are required for detection of mRNA levels (which return to base-line levels by 24 h), and incubation times in excess of 4 h are needed before protein secretion is detected. This transient expression of IL-8 is in contrast to the pattern of production by monocytes, epithelial cells and fibroblasts, which show expression that persists for up to 24 h after stimulation. IL-8 (and related NAP-like peptides) is a powerful neutrophil chemoattractant and, in combination with cytochalasin B, can induce degranulation and activation of the respiratory burst ( 3.5.5). 

A limitation of the flow cytometric binding assay has been the precise determination of the receptor affinity and calculation of the receptors per cell. This limitation appears to have been overcome by the development of fluorescein and phycoerythrin compensation-calibration standards (Flow Cytometry Standards Corp., Research Triangle Park, NC). These standards have made it possible to quantify the fluorescence intensity of samples labeled with fluorescein or phycoerythrin, and relate the intensity to molecules of equivalent soluble fluorochrome. These standards have been utilized in quantitative studies of neutrophil chemoattractant-ligand interaction (4). 

Pfister, R.R., Haddox, J.L., Sommers, C.I., Lam, K.W. A neutrophil chemoattractant is released from cellular and extracellular components of the alkali-degraded cornea and blood. Invest Ophthalmol Vis Sci 37(1), 230-237 (1996)... 

IL-8 Bone marrow, thymus (stromal cells) Neutrophils Chemoattractant... 

Blockade of a2, Pi and p2-adrenoreceptors on LPS-stimulated alveolar macrophages reduces the release of interleukin (IL)-ip, IL-6 and cytokine-induced neutrophil chemoattractant-1. In this same condition, TNFa release is also strongly reduced by a2 and p2-adrenoreceptors antagonists. However, the blockade of a2-adrenoreceptors reached the most consistent suppression of the investigated cytokines (Flierl et al., 2007). 

Zagorski, J. and Wahl, S. M. (1997) Inhibition of acute peritoneal inflammation in rats by a cytokine induced neutrophil chemoattractant receptor antagonist. J. Immunol. 159, 1059-1062. 

The failure of antioxidant mechanisms to correct redox disequilibrium could lead to the escalation of oxidative to tier 2. Tier 2 cellular responses are characterized by the activation of cellular signaling pathway such as stress-activated kinases (p38 MAP kinase and JNK) along with activation and nuclear translocation of transcription factors NF-kB and STAT-1. NF-KB-induced transcriptional activation leads to the production of a number of pro-inflammatory cytokines, including the neutrophil chemoattractant IL-8. STAT-1 activation stimulates the increased production of CXC-motif chemokines that function in lymphocyte recruitment and activation. Therefore, tier 2 oxidative responses result in an inflammatory response in the lung. 

T. Liu, P. R. Young, P. C. McDonnell, R. F. White, F. C. Barone, and G. Z. Feuerstein, Cytokine-Induced Neutrophil Chemoattractant mRNA Expressed in Cerebral Ischemia, Neuroscience Letters, 164(1993) 125-128. 

K. Watanabe, K. Konishi, M. Fujioka, S. Kinoshita, and H. Nakagawa, The Neutrophil Chemoattractant Produced by the Rat Kidney Epithelioid Cell Line NRK-52E is a Protein Related to ClNC/KC/gro Vrotem, Journal of Biological Chemistry, 264 (1989) 19559—19563. 

Y. Yamasaki, Y. Matsuo, N. Matsuura, H. Onodera, Y. Itoyama, and K. Kogure, Transient Increase of Cytokine-Induced Neutrophil Chemoattractant, A Member of the Interleukin-8 Family, in Ischemic Brain Areas After Focal Ischemia in Rats, Stroke, 26 (1995) 318-323. 

IL-8 (previously known as neutrophil activation protein-1) is a potent neutrophil chemoattractant cytokine, which may be released by a variety of airway cells (Kunkel etal., 1991), including T cells, endothelial cells, macrophages, eosinophils and epithelial cells... 

Cytokine Production/Cellular Activation TNFa and IFNy mediate the induction of other cytokines (IL-1 and IL-6) and the activation of phagocytes. It has been suggested that particle-induced expression of MIP-2 and cytokine-induced neutrophil chemoattractant CKs in the rat lung are mediated at least in part by production of TNFa. TNF is involved in control of monocyte-mediated regulation of cytokine production by T cells. Preincubation of monocytes with rTNF enhanced their ability to induce IFNy production, and TNF synthesis inhibitors decreased this induction. However, Th2 cells are stimulated in the relative absence of monocyte co-stimulatory signal(s), probably IL-6. Concerning pain responsivity, TNFa produces dose-dependent hyperalgesia mediated via the induced release of IL-lp. ... 

As indicated in Table 22-8, most of CXC CKs are attrac-tants for PMNs (neutrophils, eosinophils, and basophils) but not for monocytes. Most of the ELR-CXC molecules are potent neutrophil chemoattractants and share the CXC CK... 

Yamasaki, Y., Matsuo, Y., Matsuura, N., Onodera, H., Itoyama, Y., and Kogure, K., Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischaemic brain areas after focal ischaemia in rats, Stroke, 26, 318, 1995. 

Huang N, Wu GD. Short chain fatty acids inhibit the expression of the neutrophil chemoattractant, interleukin 8, in the Caco-2 intestinal cell line. Adv Bxp Med Biol 1997 427 145-153. 

An inflammatory mediator — neutrophil chemoattractant activates PMNs T free radical formation —> cell damage,... 

Monosubstituted Mn(ii)-based complexes, which catalyze the dismutation of superoxide as shown by stopped-flow kinetic analysis, were tested for antiinflammatory activity in the mouse acetic acid-induced colitis model. As can be seen from Table 3, all of the SOD mimics are anti-inflammatory. Histological analysis of the colonic tissue confirmed these results. Of particular importance is the observation that Mn(ii) complexes that have no SOD activity, specifically the Mn(ii) dichloro complexes of 1,4,7,10,13-pentaazacyclohexadecane and 1,4,7,11,14-pentaazacycloheptadecane, do not protect against the colonic inflammation induced by acetic acid when the compounds are administered in-tracolonically at a dose of 30mgkg These results are consistent with a role for superoxide as a mediator of neutrophil-dependent inflammation. Consistent with this hypothesis is the observation that SC-52608 inhibits neutrophil-dependent inflammation induced by the intradermal administration of leukotriene 64, a neutrophil chemoattractant. ... 

Several members of the CXC family of chemokines are well-characterized, potent neutrophil chemoattractants (table 1). CXCL8, the most well-characterized... 

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