Chemoattractants, activation

Cox JH, Dean RA, Roberts CR et al (2008) Matrix metalloproteinase processing of CXCLl 1/I-TAC results in loss of chemoattractant activity and altered glycosaminoglycan binding. J Biol Chem... 

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. 

Recently, structure-activity relationship studies of human /3-defensin have investigated the structural characteristics necessary for chemoattractive activities. Importantly, the native structure of HBD-3 has three disulfide bonds between cysteine residues C1-C5, C2-C4, C3-C6 and in this configuration is able to induce migration of CCR6 HEK293 cells at concentrations as low as lOngmPf An investigation by Wu demonstrated that... 

Neurotrophic factors play a central role in development and maintenance of neuronal cells. After release from the target cells, they bind specific receptors on the nerve termini, are internalized and carried up the axon to the perikaryon by retrograde transport. This process helps guide the direction of neurite growth (i.e. a chemoattractant activity) during neuronal development, and also serves to nourish the developing cell. Once established, the process of retrograde transport must continue if the cell is to survive and remain differentiated. 

C4. Center, D. M., and Cruikshank, W., Modulation of lymphocyte migration by human lymphokines. I. Identification and characterization of chemoattractant activity for lymphocytes from mitogen-stimulated mononuclear cells. J. Immunol. 128, 2563-2568 (1982). 

The selectins are a family of lectins that mediate the movement of leukocytes from the bloodstream into sites of inflammation. This multistep cascade proceeds by initial attachment leading to the rolling of leukoc)rtes along endothelial vasculature via selectin-carbohydrate interactions. Subsequent firm adhesion requires chemoattractant activation of leukocyte p2 integrins which mediate arrest through interaction with endothelial receptors. Leukocytes then extravasate between endothelial cells in the direction of chemoattractants as indicated in O Fig. 3 [42]. 

Human eosinophils were found to elaborate chemoattractants for lymphocytes (Lim etal., 1994). Eosinophils contained mRNA transcripts for LCF and RANTES detectable by RT-PCR amplification and released bioactive LCF neutralized both by antibodies to LCF and CD4, the LCF receptor on migrating lymphocytes (Lim et al., 1994). In addition, eosinophils released RANTES protein detectable by ELISA and by functional lymphocyte migration assay. Thus, eosinophils are a source of cytokines capable of specificaUy affecting the function of CD4 lymphocytes. The recognition that eosinophils are a source of lymphocyte chemoattractant activity identifies an additional mechanism whereby eosinophils may contribute to lymphocyte responses. Since eosinophils are recruited early in certain allergic inflammatory immune responses, the release of LCF and RANTES by human eosinophils may enable eosinophils to recruit and activate not only other eosinophils but also CD4 lymphocytes (Lim etal., 1994). 

Haslett, C., Jose, P.J., Giclas, P.C., Williams, T.J. and Henson, P.M. (1989a). Cessation of neutrophil influx in C5a-induced acute experimental arthritis is associated with loss of chemoattractant activity from joint spaces. J. Immunol. 142, 3510-3517. 

Laudanna C, Campbell JJ, Butcher EC (1996) Role of Rho in chemoattractant-activated leukocyte adhesion through integrins. In Science 271 981 -3 Machesky LM, Hall A (1996) Rho a connection between membrane receptor signalling and the cytoskeleton. In Trends Cell Biol. 6 304—10 Maehama T, Ohoka Y, Ohtsuka T et al. (1990) Botulinum ADP-ribosyltransferase activity as affected by detergents and phospholipids. In FEBS Lett 263 376-80 Malcolm KC, Ross AH, Qiu R-G etal. (1994) Activation of rat liver phospholipase D by the small GTP-binding protein RhoA. In J. Biol. Chem. 269 25951 -4 Moriishi K, Syuto B, Yokosawa N efal. (1991) Purification and characterization of ADP-ribosyltransferases (Exoenzyme C3) of Clostridium Botulinum type C and D strains. In J. Bacferiol. 173 6025-9... 

Chemokines Chemokines comprise a superfamily of small proteins that demonstrate a wide variety of biological and pathological functions [7], Many reports have shown that chemokines and their receptors regulate cell differentiation, proliferation, and migration. In this section, chemoattractant activity and small-molecular antagonists are focused on and described concisely as follows. 

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

Chemoattracts activated macrophages, thymocytes, and dendritic cells... 

Laudanna, C., Campbell, J.J. and Butcher, E.C. (1996). Role of Rho in chemoattractant-activated leukocyte adhesion through integrins. Science 271, 981-983. 

Figure 2 (left). Permeation chromatography of ESS on Bio-Gel P-2 column. Three major peaks were observed. All of the chemoattractive activity for snakes was in Peak 1, none in peaks 2 or 3. Pe 3 contained alarm pheromone for earthworms. Figure 3 (right). Polyacrylamide gel electrophoresis of ESS (B and D), purified chemoattractant (A) on non-denaturing gel protein markers (E) and purified chemoattractant (F) on SDS-denaturing gel. From Jiang et al. (1990) with permission. 

The second temperature effect takes place when the EWW is simultaneously submitted to pH and heating perturbations. The changes effected can be detected chemically and behaviorally. In 0.1 N NaOH at 37° chemoattractant activity can be detected after 30 minutes of incubation but not at 60... 

Earthworm cuticle collagen was purified by the methods of Murray et al. (1982) and Josse and Harrington (1964). Lyophilized EWC placed on an AcA 44 column produced an elution profile (Fig. 6) very similar to the elution profile of EWW (Fig. 3). Large F2 peaks and large F4 peaks were observed. Behavioral testing showed that the F2 peak contained chemoattractant activity (Fig. 7) as did the EWC prior separation on the column. 

To determine if earthworms that had been decuticlized could be used to produce chemoattractant, we removed the cuticles of 50 worms by placing the worms in anhydrous ether for 15 minutes and then stripping the cuticles from the worms (Watson, 1958). The decuticlized worms were placed in 60 C H2O for 2 minutes, discarded, and the wash water centrifuged. The supernatant was tested for chemoattractant activity as described above and found to have no chemoattractant activity. 

From control studies, we learned that periodate and ethylene glycol, separately and in mixture, behave neither as attractants nor as aversive agents for garter snakes. Treatment of EWW with different concentrations of periodate for 15 minutes at room temperature (RT) resulted in loss of chemoattractant activity at 2.8 mM periodate while at 2.1 mM periodate activity could still be detected. When the reaction time was increased to 1 hour at RT, activity was retained up to 0.83 mM periodate but lost at 1.25 mM periodate (Fig. 8). At 8.3 mM periodate at RT, inactivation was instantaneous. (The periodate concentrations shown in Fig. 8 are the concentrations used prior to dilution with EWW. In the text, final periodate concentrations are used. The equivalent values are, initial concentrations 0.1, 1.0, 10.0, 20.0, 30.0, 40.0, 50.0 mM final concentrations 0.007, 0.04, 0.42, 0.83, 1.25, 1.67, 2.1 mM, respectively.)... 

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