Abstract
The extent of pulmonary inflammation during lung injury ultimately determines patient outcome. Pulmonary inflammation is initiated by the migration of neutrophils into the alveolar space. Recent work has demonstrated that the guidance protein semaphorin 7A (SEMA7A) influences the migration of neutrophils into hypoxic tissue sites, yet, its role during lung injury is not well understood. Here, we report that the expression of SEMA7A is induced in vitro through pro-inflammatory cytokines. SEMA7A itself induces the production of pro-inflammatory cytokines in endothelial and epithelial cells, enhancing pulmonary inflammation. The induction of SEMA7A facilitates the transendothelial migration of neutrophils. In vivo, animals with deletion of SEMA7A expression showed reduced signs of pulmonary inflammatory changes following lipopolysaccharide challenge. We define here the role of SEMA7A in the development of lung injury and identify a potential pathway to interfere with these detrimental changes. Future anti-inflammatory strategies for the treatment of lung injury might be based on this finding.
Highlights
Acute lung injury (ALI) develops in response to pneumonia, major surgery or prolonged mechanical ventilation and is associated with a high mortality rate [1]
Semaphorin 7A is induced during lung injury
We have previously shown that semaphorin 7A (SEMA7A) influences polymorphonuclear leukocytes (PMN) migration during hypoxia [8]
Summary
Acute lung injury (ALI) develops in response to pneumonia, major surgery or prolonged mechanical ventilation and is associated with a high mortality rate [1]. A critical step during the early stages of lung injury is the migration of neutrophils from the vascular compartment into the alveolar space. The severity of the associated symptoms is determined by the extent of alveolar inflammation and is of key importance for the outcome of affected patients [2]. The infiltration of neutrophils and the development of inflammation within the alveolar space are controlled by classical paradigms through the chemokine system [3, 4]. Recent work has demonstrated a significant role for neuronal guidance protein signaling in the control of neutrophil migration and the orchestration of acute inflammation [5,6,7]
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