C3 as a sensitive biomarker of alveolocapillary barrier integrity in acute lung injury: Protective modulation by enoxaparin
Tissue and Cell, cilt.101, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 101
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.tice.2026.103458
- Dergi Adı: Tissue and Cell
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE
- Anahtar Kelimeler: Acute lung injury, C3, complement system, Enoxaparin, LPS
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
Enoxaparin (ENX), a low-molecular-weight heparin (LMWH) widely used for venous thromboembolism prophylaxis, has been reported to inhibit complement activation at proximal steps. Early complement activation is increasingly recognized as a key driver of alveolocapillary barrier disruption, highlighting the need for early biomarkers and prophylactic strategies in ALI. Accordingly, this study investigated local and systemic effects of ENX on C2, C3, TNF-α, and IL-8 in an LPS-induced ALI model to clarify the contribution of complement blockade to inflammatory pathogenesis. Forty-six male Wistar albino rats were randomized in four groups (SHM, ENX, LPS, and ENX+LPS) and treated with intratracheal LPS (5 mg/kg) followed by subcutaneous ENX (2 mg/kg). After six hours, BALF, serum, and lung tissues were collected. Biomarkers were quantified by ELISA; histopathological changes were evaluated using staining (H-E, MT, PAS), and immunohistochemistry for TNF-α and CC16. LPS reduced serum C3, increased BALF TNF-α, enhanced TNF-α immunoreactivity, and disrupted the alveolocapillary barrier, reflected by elevated Smith and ATS scores. ENX mitigated these alterations, preserved barrier integrity, and restricted inflammation predominantly to the interstitium. Strong correlations between C3 levels and histopathological scores underscored its central role of C3 in the progression of ALI. Conversely, C2 showed limited variation and no correlation with tissue injury. CC16 expression was reduced following LPS exposure, indicating club cell dysfunction and interstitial inflammation, with only partial recovery under ENX. Collectively, these findings identify C3 as a sensitive early biomarker of complement-driven lung injury and support early complement modulation as a promising prophylactic approach in ALI.