Complement components as potential therapeutic targets for asthma treatment

Abstract

Summary Asthma is the most common respiratory disorder, and is characterized by distal airway inflammation and hyperresponsiveness. This disease challenges human health because of its increasing prevalence, severity, morbidity, and the lack of a proper and complete cure. Asthma is characterized by TH2–skewed inflammation with elevated pulmonary levels of IL-4, IL-5, and IL-13 levels. Although there are early forays into targeting TH2 immunity, less-specific corticosteroid therapy remains the immunomodulator of choice. Innate immune injury mediated by complement components also act as potent mediators of the allergic inflammatory responses and offer a new and exciting possibility for asthma immunotherapy. The complement cascade consists of a number of plasma- and membrane-bound proteins, and the cleavage products of these proteins (C3 and C5) regulate the magnitude of adaptive immune responses. Complement protein are responsible for many pathophysiological features of asthma, including inflammatory cell infiltration, mucus secretion, increases in vascular permeability, and smooth muscle cell contraction. This review highlights the complement-mediated injury during asthma inflammation, and how blockade of active complement mediators may have therapeutic application.

Relationship of Circulating C5a and Complement Factor H Levels With Disease Control in Pregnant Women With Asthma

“…11,12,28 C5a may contribute to airway inflammation in asthma, 11,12,28 which was reflected in the correlation between C5a and F ENO levels in non-pregnant subjects with asthma in our study. Furthermore, inhibition of C5a improved lung function, airway hyperreactivity, and airway inflammation in animal models and in mild allergic asthma subjects.…”

A Double‐Edged Sword: Complement Component 3 in Toxoplasma gondii Infection

“…In other contexts, the pharmacologic interventions of complement cascade especially in C3 have been explored such as autoimmune arthritis and reactive airway disease . Our findings elicit lots of significant questions for further studies.…”

Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis

“…The mechanism that we have uncovered brings forward C3 targeting as a novel therapeutic approach for treatment of leptomeningeal metastasis. Pharmacologic intervention in C3 signaling has been explored in other contexts, including reactive airway disease (Khan et al, 2014) and autoimmune arthritis (Hutamekalin et al, 2010). The preclinical results presented here suggest that pharmacologic interference with C3 signaling is therapeutically beneficial to suppress leptomeningeal metastasis.…”