Elevated levels of peripheral‐blood, naturally occurring aliphatic polyamines in bronchial asthmatic patients with active symptoms

Abstract

The levels of peripheral-blood, naturally occurring aliphatic polyamines, such as putrescine, spermidine, and spermine, from 21 bronchial asthmatic patients (11 atopics and 10 nonatopics) were measured by postcolumn derivatization high-performance liquid chromatography analysis. None of the patients, except the 44-year-old woman in the case report below, were given prednisolone, and they were instructed to take only regular medication during the tests. Blood was drawn from the patients in a fasting state, and the polyamine levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Nine (5 atopics and 4 nonatopics), 6 (3 atopics and 3 nonatopics), and 4 (3 atopics and 1 nonatopic) out of 20 patients, when they had relatively mild asthmatic attacks, showed higher putrescine, spermidine, and spermine levels, respectively, than those of normal healthy control subjects. The levels of peripheral blood polyamines from a 44-year-old atopic bronchial asthmatic woman, who was admitted to the hospital with severe asthmatic attacks, were measured serially, and the putrescine and spermidine levels were found to be elevated during the asthmatic attacks, returning to normal levels in parallel with the clinical course. These data may suggest a role for naturally occurring aliphatic polyamines in bronchial asthma.

Genetic polymorphisms in arginase I and II and childhood asthma and atopy

“…1 Circulating levels of putrescine and spermidine were found to be elevated in patients during asthmatic attacks. 26 Proline is a rate limiting substrate for synthesis of collagen, which is deposited in the subepithelium of asthmatic airways in human beings. 27 Production of collagens in asthmatic airway cells can influence proliferation and likely can contribute to airway remodeling, a key process in asthma.…”

Increased arginase activity contributes to airway remodelling in chronic allergic asthma

“…Both arginase and ornithine decarboxylase (ODC), which converts L-ornithine into putrescine, are expressed in airway epithelial cells [42] and induction of both enzymes by growth factors, leading to increased polyamine levels, has been described [4]. Moreover, elevated polyamine levels have been detected in the lungs of allergen-challenged mice [10] and in the serum of asthmatic patients [26]. We now demonstrate that the allergeninduced increase in arginase activity causes an increased production of the polyamine putrescine, which is completely abolished by ABH.…”

“…In addition, increased arginase activity could induce airway remodelling via increased synthesis of polyamines (putrescine, spermidine and spermine) and L-proline downstream of L-ornithine [5,9,25]. Polyamines are involved in cell proliferation and differentiation [5] and increased polyamine levels have been demonstrated in allergen-challenged mice [10] and asthmatic patients [26]. L-Proline is a precursor of collagen [5] and could thus play a role in allergen-induced fibrosis.…”

Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models

“…In support of a potential role of arginase in airway fibrosis in asthma, IL-4 and -13 increase arginase I and II expression and arginase activity in cultured rat fibroblasts [114]. In addition, increased levels of polyamines have been observed in mouse lung following allergen challenge [127] and in the serum of asthmatic patients [133], respectively. A role for decreased NO synthesis in airway remodelling can also be envisaged, since NO inhibits proliferation of airway smooth muscle cells [134].…”