Chemotaxis mechanisms

This section will focus on receptor tyrosine kinase-mediated chemotac-tic responses of mesenchymal cells. G-protein-coupled receptor-mediated chemotaxis mechanisms were discussed above in the Dictyostelium section. 

Table 2 summarizes the behavioral mechanisms of chemotaxis in the systems reviewed in this book. If these systems faithfully represent the mechanisms of chemotaxis in nature, it appears that prokaryotes mainly employ trial-and-error chemotaxis mechanisms— the phobic response and klinokinesis, defined in Table 2 and, in more detail, in Chapter 1. In contrast, eukaryotes appear to primarily employ the more direct mechanism—modulation of the direction of movement according to the stimulant gradient. A number of non-mutually-exclusive reasons may account for this difference. First, the mechanisms employed by bacteria... 

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). 

As already mentioned, molecular cross talk seems to be the prerequisite mechanism for most of root microbial infections. Indeed the initial step of any root colonization involves the movement of microbes to the plant root surface bacterial movement can be passive, via soil water flux, or active, via specific induction of flagellar activity by plant released compounds (chemotaxis) (Chaps. 4 and 7). Other important steps are adsorption and anchoring to the root surface. 

Links, J. An hypothesis for the mechanism of (phobo-) chemotaxis. II. The carotenoids, steroids and fatty acids of Polytoma uvella. Thesis, Leiden, 1955... 

Mechanisms of Complement Activation. Complement is a major mediator of the inflammatory response. Complement recruits and enlists the participation of humoral and cellular effector systems, induces histamine release from mast cells and directs migration of leukocytes (chemotaxis), in addition to producing phagocytosis and the release of lysosomal constituents from phagocytes. 

Involvement of complement activation in the etiology of the acute byssinotic reaction could explain the pathogenic mechanism of histamine release, non-histamine-mediated bronchoconstriction, chemotaxis, endotoxin and bacterial proteolytic enzyme action. Bronchoconstriction experienced in the acute byssinotic reaction might be attributed to the combined action of C3a and C5a mediated histamine release and non-histamine mediated kinin activity. The presence of PMN in the nasal airways of byssinotics might be explained by the chemotactic action of C5a and the C567 complex. 

Potential etiologic agents in cotton dust that release histamine are shown in Table VII. Some of these are effector molecules having potent biological effects in minute concentrations, i.e. peptides, which may act directly to affect chemotaxis and leukocyte recruitment, and also to release histamine and stimulate respiratory smooth muscle contraction. These bifunctional effector molecules are of major importance in considering pathogenic mechanisms in byssinosis. 

Migration of cells in response to stimuli is responsible for several physiological functions mostly in the case of inflammatory responses and immune functions. The transwell chemotaxis assay is useful to study mechanisms of migration during chemotaxis. The main purpose of this assay is to determine if a molecule of interest exhibits chemotactic activity. Molecules that... 

NSAID treatment alone. They may be used concurrently with NS AIDS. It mostly takes 1-3 month for their anti-inflammatory action to become apparent. The pharmacodynamics of these antimalarials in RA is uncertain. Possible mechanisms include decreased leukocyte chemotaxis, stabilization of lysosomal membranes, inhibition of DNA and RNA synthesis and trapping of free radicals. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

The anti-inflammatory activity of the NSAIDs is mediated chiefly through inhibition of biosynthesis of prostaglandins (Figure 36-2). Various NSAIDs have additional possible mechanisms of action, including inhibition of chemotaxis, down-regulation of interleukin-1 production, decreased production of free radicals and superoxide, and interference with calcium-mediated intracellular events. Aspirin irreversibly acetylates and blocks platelet cyclooxygenase, while most non-COX-selective NSAIDs are reversible inhibitors. 

Chloroquine and hydroxychloroquine are used mainly in malaria (see Chapter 52) and in the rheumatic diseases. The mechanism of the antiinflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals. 

Methotrexate s principal mechanism of action at the low doses used in the rheumatic diseases probably relates to inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase and thymidylate synthetase, with secondary effects on polymorphonuclear chemotaxis. There is some effect on dihydrofolate reductase and this affects lymphocyte and macrophage function, but this is not its principal mechanism of action. Methotrexate has direct inhibitory effects on proliferation and stimulates apoptosis in immune-inflammatory cells. Additionally, inhibition of proinflammatory cytokines linked to rheumatoid synovitis has been shown, leading to decreased inflammation seen with rheumatoid arthritis. 

FIGURE 12-26 The two-component signaling mechanism in bacterial chemotaxis. When an attractant ligand (A) binds to the receptor domain of the membrane-bound receptor, a protein His kinase in the cytosolic domain (component 1) is activated and autophosphorylates on a His residue. This phosphoryl group is then transferred to an Asp residue on component 2 (in some cases a separate protein in others, another domain of the receptor protein). After phosphorylation on Asp, component 2 moves to the base of the flagellum, where it determines the direction of rotation of the flagellar motor. 

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