Complement components as potential therapeutic targets for asthma treatment.
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 T(H)2-skewed inflammation with elevated pulmonary levels of IL-4, IL-5, and IL-13 levels. Although there are early forays into targeting T(H)2 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.
Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates. Electronic address: makhan@sharjah.ac.ae.
Mohammad Afzal
MA
Khan
Division of Pulmonary and Critical Care Medicine, VA Palo Health Care System, Stanford University, School of Medicine, Palo Alto, CA, USA.
Mark R
MR
Nicolls
Innovative Bio-Medical Technologies Ltd, Toronto, Canada.
Besiki
B
Surguladze
Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Ismail
I
Saadoun
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015926:Complement C3a / Q000096:biosynthesis; D015936:Complement C5a / Q000096:biosynthesis; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D058990:Molecular Targeted Therapy / Q000379:methods
D018927:Anti-Asthmatic Agents; D051056:Complement Inactivating Agents; D015926:Complement C3a; D015936:Complement C5a; D003165:Complement System Proteins
Anaphylatoxins; Asthma; Complement mediated injury