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| Item Type: | Article |
|---|---|
| Title: | Carboxypeptidase M deficiency aggravates complement-induced lung injury |
| Creators: |
Qadri, Fatimunnisa |
| Abstract: | Carboxypeptidase M (CPM) metabolizes several bioactive peptides by removing their C-terminal arginine residues. It was postulated that the substrates include the anaphylatoxins C3a and C5a generating their less active desArg forms. C3a and C5a are potent mediators of inflammation, shaping both innate and adaptive immune responses. Considering that CPM is a membrane-bound enzyme expressed in multiple organs, we hypothesized that it may protect tissues from anaphylatoxin-driven damage. Using mass spectrometry, we confirmed that CPM efficiently converts C3a and C5a into their desArg forms. We then generated CPM-deficient rats and subjected them to a complement-dependent model of acute lung injury. Compared to controls, CPM-deficient rats exhibited consistently exacerbated lung damage, including higher histological injury scores, increased neutrophil and macrophage infiltration, and elevated expression of inflammatory marker genes. These findings indicate that CPM protects the lung from complement-mediated injury and highlight it as a potential therapeutic target in inflammatory diseases. |
| Keywords: | Anaphylatoxins, Carboxypeptidases, Acute Lung Injury, Rat Model, Animals, Rats |
| Source: | iScience |
| ISSN: | 2589-0042 |
| Publisher: | Cell Press |
| Volume: | 29 |
| Number: | 9 |
| Page Range: | 117463 |
| Number of Pages: | 1 |
| Date: | 18 September 2026 |
| Official Publication: | https://doi.org/10.1016/j.isci.2026.117463 |
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