Allen P. Kaplan, MD and Berhane Ghebrehiwet, DVM, DSc

 

The beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects lung alveolar type II epithelial calls by attaching to angiotensin-converting enzyme 2 (ACE-2) expressed at the cells’ surface via its viral spike protein.1A transmembrane serum protease (TMPRSS2) activates the viral spike protein and enables cell entry. The more severe manifestations of the resultant inflammatory response include dry cough, dyspnea, tachypnea, a feeling of drowning, pulmonary edema, unilateral or bilateral pneumonia, mottling and ground-glass opacifies on computed tomography scan, and progression to the acute respiratory distress syndrome requiring ventilatory support.2 Hypoxemia is particularly prominent throughout, and a hyaline membrane of dead cells can be observed at autopsy. Once infection takes hold, a cascade of inflammatory events is initiated including the release of cytokines such as IL-1, IL-6, IP-10, MCP-1, TNF-α,3and many more, which has been referred to as a “cytokine storm.” In addition, the prominent edema seen throughout the lung and the association of ACE inhibition with severe angioedema has focused attention on another innate inflammatory cascade, namely, the overproduction of bradykinin,3which is the focus of this editorial.

There are 2 general pathways for the production of bradykinin, the first being the release of cellular tissue kallikrein, which cleaves low-molecular weight kininogen (LK or LMWK) to release lys-bradykinin (Fig 1 ). Tissue kallikrein is secreted as an active enzyme (ie, processed intracellularly) and is a particularly prominent product of the lung, pancreas, kidney, salivary glands, and the prostate. There are 15 homologous gene products, 3 of which can produce bradykinin (KLK 1, 2, and 12), with KLK1 being the most prominent.

Read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598417/