Chemotactic agents

White blood cell preferentially located near potential entry sites for microbial pathogens and specialized for the uptake of particulate material by phagocytosis. Most macrophages originate from peripheral blood monocytes and are able to leave the circulation following stimulation by chemotactic agents. 

To explore the operation of the simple model of development, an artificial organism was evolved, one that simulates a chemotactic agent an agent that... 

Recruited blood monocytes encountering local elevated levels of Ap peptide would then refold the Ap into a fibrillar conformation, thus forming the core of an NP adjacent to a blood vessel [24]. These plaque-bound monocytes differentiate into macrophages and mount an aberrant "wound response" through the release of neurotrophic and chemotactic agents, inducing an inappropriate ectopic sprouting response toward the... 

Figure 4.8. Hypothesis for the local generation of mast-cell-stimulating peptides by the action of neutrophil-derived enzymes on albumin. Initial stimulation of the mast cell by any of a variety of agents causes the release of preformed histamine (H) neutrophil and eosinophil chemotactic factors (NCF, ECF) and enzymes and the de novo synthesis of prostaglandins (PG) and leukotrienes (LT). These agents increase vascular permeability and vessel diameter. As a result, albumin and later neutrophils (PMN) enter the tissue space where the latter undergo phagocytosis and the secretion of proteolytic enzymes to the extracellular space where they act on albumin to generate NRP (neurotensin-related peptide) and HRP (histamine-releasing peptide). These newly formed peptides then act as a second stimulus to the mast cell. In addition NRP and HRP may affect other immunocompetent celt such as monocytes, macrophages or eosinophils.

Since cellular immunity results in the release of chemotactic lymphocytes that in turn enhance phagocytosis, a deficiency in cellular immunity may also result in chronic infections. Cellular immunity is mediated by T cells, macrophages, and NK cells involved in complex compensatory networks and secondary changes. Immunosuppressive agents may act directly by lethality to T cells, or indirectly by blocking mitosis, lymphokine synthesis, lymphokine release, or membrane receptors to lymphokines. In addition, cellular immunity is involved in the production and release of interferon, a lymphokine that ultimately results in blockage of viral replication (Table 15.4). Viruses are particularly susceptible to cytolysis by T cells since they often attach to the surface of infected cells. Thus, immunosuppression of any of the components of cellular immunity may result in an increase in protozoan, fungal, and viral infections as well as opportunistic bacterial infections. 

The role of microtubules in neutrophil function can be investigated using agents such as colchicine, colcemid, vinblastine and vincristine, which disrupt these structures. Stimulation of neutrophils with chemotactic agents causes a rapid and transient assembly of microtubules, but this assembly does not affect chemotaxis. Similarly, cytoplasts (neutrophils devoid of nu-... 

Invasion of the tissues by an infective agent initiates an inflammatory response in the animal. This is non-specific and is mediated primarily by substances released from tissues that are damaged as a result of either trauma or the toxic effects of the infective agent. The major mediator is the vasoactive amine histamine, which causes an increased local blood flow and capillary permeability, resulting in local oedema. A major aspect of the inflammatory response is the involvement of large numbers of phagocytic cells, particularly the polymorphonuclear leucocytes. These are chemotactically attracted to the inflamed tissues and are mainly responsible for the elimination of particulate material. This often results in the destruction of many of these cells and the formation of pus. 

Inhibition of leucocyte adhesion to endothelium. By acting on the gene transcription factor called nuclear factor kappa B (NFkB), NO limits the expression by endothelial cells of monocyte chemotactic protein-1 (MCP-1) and VCAM-1. As both MCP-1 and VCAM-1 are involved with pro-inflammatory responses, NO is in this manner an anti-inflammatory agent ... 

It is postulated that chemotactic agents leach from respirable cotton dust particles in the small bronchioles. AECD recruit PMNs to the lung in the following sequence connective tissue beneath the basal lamina, between airway cells, and, finally, into the lumen. Chest tightness is also correlated with leucocyte recruitment (41). Although it has been proposed that extracellular lysosomal enzymes from PMNs cause the symptoms of byssinosis by initiating release of histamine and/or other chemical mediators (25), it has not been shown that cotton dust actually liberates hist j. jjfg m j y... 

Chemotactic Agents in Extracts of Cotton Mill Dust... 

Mast cells are large cells located immediately outside capillaries in many organs, including the lungs. As basophils, mast cells can release histamine or leukotriene B4, a potent chemotactic agent. 

Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area (Fig. 37.1).The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area. 

Chemotactic agents such as neutrophils can escape from capillaries and attracts macrophages to destroy antigenic materials. 

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