Chemoattractants are small soluble molecules which have been widely used in research to aid the investigation of cell motility.
Chemoattractants generally induce directed cell migration upon binding to specific cell surface receptor(s), this in turn activates several intracellular signaling pathways. Ultimately, the movement of cells towards a chemoattractant requires the critical reorganization of cellular actin cytoskeletal components.
The principle behind utilizing chemoattractants in research is straightforward, cells with migratory capacity move in the direction (chemotaxis) towards a higher concentration of a chemoattractant.
Chemotaxis of a given cell is specific to the chemoattractant agent used as well as the surface receptors the cells express. Henceforth, chemoattractant agents have been exploited to gain insight into various physiological processes and functions.
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The use of Chemoattractants to Explore Mechanisms in Asthma
Asthma is a chronic disease characterized by airway inflammation and airflow obstruction. These hallmarks are regulated by cells of the innate and adaptive immune system, in combination with structural airway cells. The recruitment of such cells to the lungs is coordinated by chemokines and/or chemokine receptors.
Therefore, inhibition of pathological locomotion of airway cells elicited via chemokines could potentially be of therapeutic significance for the treatment of asthma. However, to develop such treatments, it is pivotal to understand the mechanisms involved in the migration of airway/immune cells to the lungs. Therefore, chemoattractants are commonly applied to achieve this.
A study conducted by Venge et al., (1996) employed chemoattractant molecules i.e. interleukins and RANTES (regulated on activation, normal T cell expressed and secreted) to examine eosinophil migration into the lungs of asthmatic subjects.
Whereas, the migration of human mast cells towards CXCL10 (chemoattractant), in the presence of specific inhibitors was investigated by Cruse et al., (2006) to deepen our knowledge on the receptors utilized by mast cells leading to the pathogenesis of asthma.
The use of Chemoattractants to Explore Mechanisms in Cancer
A variety of chemoattractants have also been used in research to aid the discovery of several molecules/mechanisms involved in increasing the invasiveness and metastasis of tumor cells, for example, chemokines and growth factors.
In addition to this, chemoattractants have also enabled researchers to decipher the interactions between host cells and tumor cells which eventually lead to tumor growth.
Several assays have been developed to test the migratory capacity of tumor cells towards specific chemoattractants, one such example is the Boyden chamber. Boyden chamber assays have been used widely to determine what molecules promote the motility of tumor cells since migration is key for metastatic dissemination of tumor cells.
The use of such in vitro techniques in research has made a substantial contribution to the field of tumor cell migration, thus allowing the recognition of a variety of signaling pathways that partake in tumor metastasis. The use of chemoattractants to pinpoint vital molecular mechanisms that promote the migratory capacity of tumor cells could also potentially facilitate the development of targeted therapy to suppress tumor growth.
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The use of Chemoattractants to Explore Mechanisms in Inflammation
Chemoattractants have also been utilized in experiments to determine the role of immune cells in inflammation. Inflammatory chemokines were identified to serve as chemoattractants for leukocytes which in turn was found to orchestrate the recruitment of numerous cells including neutrophils and monocytes to the site of inflammation/infection.
In addition to this, a diverse range of secretory chemicals has previously been tested to determine the various chemoattractant agents that influence the recruitment of leukocytes from the blood circulation into extravascular and to determine the receptors involved. Indeed, leukocytes were found to express several receptors for various chemoattractant agents including complement proteins and lipid mediators.
The identification of specific chemoattractants for leukocytes has helped to determine the functional role of compounds in inflammation. Moreover, the identification of such chemoattractants has been proposed to perhaps impact the development of therapeutic options targeting particular molecules for the treatment of inflammatory diseases.
Chemoattracts Aiding the Discovery of Cellular Functions
Besides the role of chemoattractants in determining molecular mechanisms in various diseases, they have also been applied to establish novel cellular functions. Platelets, a cellular component of blood, was initially thought to be immotile cells largely owing to their lack of a nucleus.
However, studies conducted by Lowenhaupt, and co-workers (1973) discovered the cells to encompass migratory capacity through the use of chemoattractants such as fibrinogen and collagen which they incorporated into a chemotaxis assay.
The detection of platelets as cells with a migratory capacity that moves towards a gradient of protein opened many avenues for investigation for researchers including the role of platelets as immune cells.
Conclusion
The application of chemoattractants in research has broadened our knowledge into the pathomechanisms of various diseases as well as a myriad of physiological processes.
Consequently, it has opened up the possibility to develop an array of targeted treatments which in turn could drastically decrease the rate of morbidity and mortality worldwide. Thus, reinforcing the application of chemoattractants to be pivotal in research.
References:
- Cruse, G. et al. (2006) ‘Functional KCa3.1 K+ channels are required for human lung mast cell migration’, Thorax. BMJ Publishing Group, 61(10), pp. 880–885. doi: 10.1136/thx.2006.060319.
- Lowenhaupt, R. W., Miller, M. A. and Glueck, H. I. (1973) ‘Platelet migration and chemotaxis demonstrated in vitro’, Thrombosis Research. Pergamon, 3(5), pp. 477–487. doi: 10.1016/0049-3848(73)90110-2.
- Venge, J. et al. (1996) Identification of IL-5 and RANTES as the major eosinophil chemoattractants in the asthmatic lung, J Allergy Clin Immunol.
Further Reading
Comprehensive Review of Intracellular Checkpoints in NK Cell Biology and Cancer