What’s new in asthma pathophysiology and immunopathology?

Abstract

Research on asthma pathophysiology over the past decade has expanded the complex repertoire involved in the pathophysiology of asthma to include inflammatory, immune and structural cells, as well as a wide range of mediators. Studies have identified a role for connective and other mesenchymal tissues involved in airway remodeling. Recent findings have implicated the innate immune response in asthma and have revealed interesting patterns of interaction between the innate and adaptive immune response and the associated complex chronic inflammatory reaction. New immune cell populations have also been added to this repertoire, including Tregs, natural killer T cells and Th17 cells. The role of the eosinophil, a prominent pathological feature in most asthma phenotypes, has also been expanding to include roles such as tissue modifiers and immune regulators via a number of fascinating and hitherto unexplored mechanistic pathways. In addition, new and significant roles have been proposed for airway smooth muscle cells, fibroblasts, epithelial and endothelial cells. Tissue remodeling is now considered an integral element of asthma pathophysiology. Finally, an intricate network of mediators, released from both immune and inflammatory cells, including thymus stromal lymphopoietin and matrix metalloproteinases, have added to the complex milieu of asthma immunity and inflammation. These findings have implications for therapy and the search for novel strategies towards better disease management. Sadly, and perhaps due to the complex nature of asthma, advances in therapeutic discoveries and developments have been limited. Thus, understanding the precise roles played by the numerous dramatis personae in this odyssey, both individually and collectively within the context of asthma pathophysiology, continues to pose new challenges. It is clear that the next stage in this saga is to embark on studies that transcend reductionist approaches to involve system analysis of the complex and multiple variables involved in asthma, including the need to narrow down the phenotypes of this condition based on careful analysis of the organs (lung and airways), cells, mediators and other factors involved in bronchial asthma.

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

“…Because Th 2 cytokines such as those quantified in this study are related to recruitment of mast cells, maturation of eosinophils, IgE synthesis and cell mobilization in allergic asthma [29], and considering that elevated levels of inosine are found at inflamed sites [4,32], we have inferred possible auto-control of allergic lung inflammation that might be mediated by purines, however, through a mechanism that seems to be independent of A 2A or A 2B receptor activation, since ZM241385 and alloxazine did not interfere with the effects of inosine on IL-4 and IL-5 levels.…”

“…The research on asthma over the past decade has expanded the complex repertoire involved in its The difference between groups was determined by ANOVA followed by Newman-Keuls multiple comparison test *P<0.001 when compared to basal group pathophysiology to include inflammatory, immune and structural cells as well as a wide range of mediators [29]. Some studies have been shown that adenosine is a proinflammatory mediator involved in the pathogenesis of asthma [7], since recent research have demonstrated that elevated levels of adenosine induces bronchoconstriction and was found in the airways of patients with asthma [7,30].…”

Assembly of a Three-Dimensional Multitype Bronchiole Coculture Model Using Magnetic Levitation

“…Thus, this model has great potential for research into airway remodeling associated with asthma. [57][58][59] That these cell types alone can create an intact matrix merits further investigation into the genesis and progression of matrix formation in the lung, and the importance of their interactions with other cell types in this process. It is also worth noting that the discovery of the potential of PFs and SMCs alone to generate the extracellular matrix would not have been possible in 2D, since in 2D stains, positive collagen type I and laminin stains localized around the cell.…”

Lung Pathologies in a Chronic Inflammation Mouse Model Are Independent of Eosinophil Degranulation

“…The long-held view of asthma as a quintessential chronic allergic disease (3,4) accompanied by eosinophil-mediated airway inflammation linked with increased levels of T-helper cell type 2 (Th2)-derived cytokines is being reinterpreted in light of the realization that the underlying immune responses in these patients are much more diverse (reviewed in References 2,[5][6][7][8]. Moreover, eosinophil targeting therapies have been efficacious only in a narrow subgroup of eosinophilic asthma patients with lower use of steroids and decreased exacerbation events as the most significant end point measures (9)(10)(11)(12).…”