Chemotactic stimuli response

Cells respond to some extracellular factors such as leukotriene B (Ford-Hutchin-son et al., 1980) by increasing the locomotion rate in an undirected manner as opposed to chemotaxis. This mechanism, known as chemokinesis, is likely on purely statistical grounds to result in cells accumulating at the site of origin of this stimulus (Wilkinson, 1987). The differentiation of factors that are chemotactic from chemokinetic responses can be difficult, but this has been greatly facilitated using the Boyden chamber (Lackie, 1986). 

Debes GF, Dahl ME, Mahiny AJ, et al. Chemotactic responses of IL-4-, IE-10-, and IFN-gamma-producing CD4+ T cells depend on tissue origin and microbial stimulus. J Immunol 2006 176(l) 557-566. 

Fig. 4. Translocation of CRAC-GFP in chemotactic Dictyostelium cells, (a) Response to a uniform stimulus of cAMP, generated as illustrated in Fig. 2a. Translocation occurs around the entire perimeter of the cell, (b) Directional response to a gradient of cAMP, generated as illustrated in Fig. 3a. The gradient direction is from bottom (low concentration) to top (high concentration). Translocation occurs preferentially at the side of the cell toward higher cAMP concentrations. Reproduced with permission from ref. 1. Copyright 2007 American Chemical Society.

Following the finding that the gradient sensed by bacteria is temporal, time-dependent studies of the chemotactic response were carried out. These studies revealed that, like many other sensory systems, the chemotactic response involves two processes excitation and adaptation (for a review, see [685]). When bacteria are stimulated, the direction of flagellar rotation and, hence, their swimming mode are changed instantaneously. This rapid, initial process, termed excitation, is completed within 0.07 s or less [320, 350, 354]. Later on, the bacteria resume their prestimulus behavior, even though the stimulus is still present. This... 

As noted previously, the evidence for the contribution of microtubules to amoeboid cell motility and chemotaxis is mixed [242]. The microtubule organizing center has been reported to be localized to either the front or rear side of the nucleus, depending upon the cell type [167, 187, 188]. Alterations in microtubules can affect fibroblast lamellipod extension and motility [150], but in some assays, chemotactic responses may be unaffected [202]. Alterations in acetylation enhance chemotactic ability [98]. Microtubules have been proposed to alter the stability of adhesion sites, enhancing their disassembly [II9]. In sum, microtubules are likely to be permissive for amoeboid motility and chemotaxis, and respond to polarization of the cell generated by the actin system with polarization of the microtubule system. This may in turn stabilize cell polarity and enhance overall chemotactic efficiency. In the absence of a strong external stimulus, or in cases in which autocrine secretion influences cell polarization, the microtubule apparatus may provide critical signals for cell polarity [164]. 

An additional indirect assay of neutrophil motility is the actin polymerization assay. Chemoattractants induce a rapid, transient actin polymerization response in neutrophils (reviewed in [289, 391]), and since actin polymerization is required for migration to occur, it is often used as an indication of chemotactic capability. Several approaches have been developed to measure this response (reviewed in [289, 391]) (Table 2). Most commonly, cells in suspension are mixed with a putative chemoattractant then fixed and stained with a fluorescent phaUotoxin that binds to polymerized actin, but not monomeric actin. The bound fluorescence is quantified using flow cytometry or spectrofluorometry. The actin polymerization response to many neutrophil chemoattractants is rapid, reaching a maximum within 10 s of stimulus addition at 37° C. As with the cell polarization assay, no information about the migratory properties of the cells is obtained with the actin polymerization assay, only the likelihood of chemotactic activity is assessed. Like the cell polarization assay, the actin polymerization assay is useful for initial screening of chemoattractants, but must be followed up with an actual measurement of motility. 

Simehowitz, L., Atkinson, J.P. and Spilberg, 1. (1980). Stimulus-specific deactivation of chemotactic factor-induced cyclic AMP response and superoxide generation by human neutrophils./. Clin. Invest. 66, 736-747. 

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