Mucus and fibrin disulfide bonds (S-S bonds)

Mucus and fibrin disulfide bonds are the primary covalent cross-links responsible for the structural integrity and high viscosity of pathological secretions in the airways. In the respiratory tract, mucin glycoproteins such as MUC5AC and MUC5B form massive polymers through disulfide bridges between their cysteine-rich terminal domains (C. Rogers, 'Physiology of airway mucus secretion and clearance', 2007). During inflammation, fibrinogen from plasma can enter the airways and be converted to fibrin, which further reinforces the mucus matrix through its own disulfide-linked network, creating a 'fibrin-rich' mucus that is exceptionally difficult to clear (S.K. Cho et al., 'Fibrin-rich mucus in COVID-19', 2020). Therapeutic agents known as mucolytics, most notably N-acetylcysteine, target these bonds by providing free sulfhydryl groups that participate in thiol-disulfide exchange reactions (A. Sadowska et al., 'Antioxidant and mucolytic properties of N-acetylcysteine', 2006). This chemical reduction breaks the large polymers into smaller, less viscous subunits, thereby facilitating expectoration and improving airflow in patients with obstructive lung diseases like cystic fibrosis and COPD.

Other names

Mucin disulfide bridgesFibrin disulfide cross-linksIntermolecular disulfide bondsCystine bridges in mucus

Reduction of disulfide bonds via thiol-disulfide exchange, converting covalent cross-links into free sulfhydryl groups to decrease polymer molecular weight and viscosity.