Anti-Semaphorin-7A single chain antibody demonstrates beneficial effects on pulmonary inflammation during acute lung injury

摘要

Pulmonary inflammation is a primary characteristic of lung injury initiated by the accession of immune cells into the alveolar space. Neutrophil migration serves an important role in pulmonary inflammation mediated by the migration of neutrophils into hypoxic tissue sites. The elimination of pulmonary inflammation is directly associated with rehabilitation in patients with lung injury. Anti-inflammatory treatment is essential following lung injury and ultimately determines patient outcomes. Semaphorin-7A (SEMA-7A) is a member of the Semaphorin family that influences the migration of neutrophils into hypoxic tissue sites, thus promoting inflammation. However, understanding of the role of SEMA-7A serves during lung injury is limited and the immunological function of SEMA-7A during the migration of neutrophils into acute injury sites remains unknown. The present study investigated SEMA-7A expression and constructed a single chain antibody for SEMA-7A (Anti-SEMA-7A) to study its therapeutic efficacy against pulmonary inflammation in a mouse model of acute injury sites. The data indicated that the expression of SEMA-7A was upregulated due to induction by pro-inflammatory cytokines and demonstrated that Anti-SEMA-7A inhibited SEMA-7A expression in vitro and in vivo. The current study also indicated that the production of pro-inflammatory cytokines induced by SEMA-7A in endothelial and epithelial cells enhanced pulmonary inflammation. Anti-SEMA-7A suppressed the transendothelial migration of neutrophils mediated by SEMA-7A. Anti-SEMA-7A treatment neutralized SEMA-7A expression and reduced signs of pulmonary inflammation, leading to the elimination of pulmonary inflammation in rat with acute lung injury. The current study identified Anti-SEMA-7A as a potential agent to interfere with the inflammatory pathway during acute lung injury, which may be the basis for anti-inflammatory strategies to treat lung injuries in the future.