Complement mediators: key regulators of airway tissue remodeling in asthma

Abstract

The complement mediators are the major effectors of the immune balance, which operates at the interface between the innate and adaptive immunity, and is vital for many immunoregulatory functions. Activation of the complement cascade through the classical, alternative or lectin pathways thus generating opsonins like C3b and C5b, anaphylatoxins C3a and C5a, chemotaxin, and inflammatory mediators, which leads to cellular death. Complement mediators that accelerate the airway remodeling are not well defined; however, an uncontrolled Th2-driven adaptive immune response has been linked to the major pathophysiologic features of asthma, including bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The mechanisms leading to complement mediated airway tissue remodeling, and the effect of therapy on preventing and/or reversing it are not clearly understood. This review highlights complement-mediated inflammation, and the mechanism through it triggers the airway tissue injury and remodeling in the airway epithelium that could serve as potential targets for developing a new drug to rescue the asthma patients.

Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

“…Each full scan was followed by 26 MS/MS fragmentation scans using variable isolation windows with 30,000 resolution at 200 m/z, automatic gain control target 3e6, and a maximum injection time of 50 ms. The 26 variable isolation windows had the following consecutive m/z: 33,26,22,20,20,18,20,19,19,19,19,20,21,21,23,23,24,26,31,32,37,40,53,66,99, and 574.…”

Complement factor and T-cell interactions during alloimmune inflammation in transplantation

“…C3 is a central molecule in the complement cascade and a potent mediator of transplant injury during alloimmune reaction . After C3 splitting through C3 convertase, C3a mediates cellular interactions, while C3b molecule generates C4b2a3b/C3bBbC3b (C5 convertase) in the individual activation pathway, respectively . Both C5 convertase components later process the splitting of C5 into C5a and C5b molecules .…”

“…6,7 After C3 splitting through C3 convertase, C3a mediates cellular interactions, while C3b molecule generates C4b2a3b/C3bBbC3b (C5 convertase) in the individual activation pathway, respectively. 2,3,32 Both C5 convertase components later process the splitting of C5 into C5a and C5b molecules. 3,4 The generated C5a is the most potent anaphylatoxin, while opsonin C5b participates in the construction of the MAC.…”

“…The complement cascade is a vast collection of secreting plasma‐ and membrane‐bound proteins, which are produced by liver hepatocytes, and to some extent are produced by endothelial cells, mesangial cells, glomerular epithelial cells, and tubular epithelial cells . The complement cascade is unique in targeting actions and routinely defends foreign antigens by the activated peptides, and their terminal complexes, which result in a massive amplification of the alloimmune reaction . Molecular signaling between activated complement mediators and inflammatory cells is critical to further amplify an effective immune response to foreign bodies, which play a leading role in transplant‐associated injuries and chronic rejection .…”

“…1 The complement cascade is unique in targeting actions and routinely defends foreign antigens by the activated peptides, and their terminal complexes, which result in a massive amplification of the alloimmune reaction. [2][3][4][5] Molecular signaling between activated complement mediators and inflammatory cells is critical to further amplify an effective immune response to foreign bodies, which play a leading role in transplant-associated injuries and chronic rejection. 6,7 During an effective alloimmune reaction, activated immune cells mount a massive inflammatory environment via inflammatory mediators (cytokines, leukotrienes), and through interactions with various cleaved products (C3a and C5a) of complement cascade.…”