Abstract
Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma. In various studies, polyamines were found to potentiate the pathogenic potential of inflammatory cells, such as mast cells and granulocytes (eosinophils and neutrophils), by either inducing the release of their pro-inflammatory mediators or prolonging their life span. Additionally, polyamines were crucial in the differentiation and alternative activation of macrophages, which play an important role in asthma pathology. Importantly, polyamines cause airway smooth muscle contraction and thus airway hyper-responsiveness, which is the key feature in asthma pathophysiology. High levels of polyamines in asthma and their active cellular and macromolecular interactions indicate the importance of the polyamine pathway in asthma pathogenesis; therefore, modulation of polyamine levels could be a suitable approach in acute and severe asthma management. This review summarizes the possible roles of polyamines in different pathophysiological features of asthma.
Highlights
Polyamines were discovered late in the 16th century as crystals in human semen by Antonie van Leeuwenhoek [1]
Spermine was the most active polyamine followed by spermidine; putrescine was ineffective in inducing survival of eosinophils
To study the role of neutrophils in asthma, neutrophils from the blood of asthmatics are stimulated with FMLP or phorbol myristate acetate (PMA) to induce an oxidative burst [50], followed by the addition of different chemicals to be tested for their effects on neutrophils
Summary
Polyamines were discovered late in the 16th century as crystals in human semen by Antonie van Leeuwenhoek [1]. These positively charged polyamines interact with negatively charged molecules in a cell such as DNA, RNA, proteins, and proteoglycans; polyamines are involved in a myriad of biological processes [3,4] They are involved in the processes that play important roles in cell survival or death pathways, such as proliferation, differentiation, autophagy, apoptosis and translation [5,6,7,8]. Polyamines are thought to be required for cell proliferation and growth and high levels of polyamines have been observed in multiple cancerous conditions [9] Their levels decline with aging, where replicative senescence of cells plays an important role [6,10]. The outcomes from various studies indicate that the polyamine pathway may play a decisive role and could be an important therapeutic target in different phenotypes of asthma such as acute and severe asthma
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