Neutrophils and IL-1α Regulate Surfactant Homeostasis during Cigarette Smoking.
J Immunol
; 206(8): 1923-1931, 2021 04 15.
Article
en En
| MEDLINE
| ID: mdl-33722877
Cigarette smoke exposure induces inflammation marked by rapid and sustained neutrophil infiltration, IL-1α, release and altered surfactant homeostasis. However, the extent to which neutrophils and IL-1α contribute to the maintenance of pulmonary surfactant homeostasis is not well understood. We sought to investigate whether neutrophils play a role in surfactant clearance as well as the effect of neutrophil depletion and IL-1α blockade on the response to cigarette smoke exposure. In vitro and in vivo administration of fluorescently labeled surfactant phosphatidylcholine was used to assess internalization of surfactant by lung neutrophils and macrophages during or following cigarette smoke exposure in mice. We also depleted neutrophils using anti-Ly-6G or anti-Gr-1 Abs, or we neutralized IL-1α using a blocking Ab to determine their respective roles in regulating surfactant homeostasis during cigarette smoke exposure. We observed that neutrophils actively internalize labeled surfactant both in vitro and in vivo and that IL-1α is required for smoke-induced elevation of surfactant protein (SP)-A and SP-D levels. Neutrophil depletion during cigarette smoke exposure led to a further increase in SP-A levels in the bronchoalveolar lavage and increased IL-1α, CCL2, GM-CSF, and G-CSF release. Finally, macrophage expression of Mmp12, a protease linked to emphysema, was increased in neutrophil-depleted groups and decreased following IL-1α blockade. Taken together, our results indicate that neutrophils and IL-1α signaling are actively involved in surfactant homeostasis and that the absence of neutrophils in the lungs during cigarette smoke exposure leads to an IL-1α-dependent exacerbation of the inflammatory response.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína A Asociada a Surfactante Pulmonar
/
Proteína D Asociada a Surfactante Pulmonar
/
Interleucina-1alfa
/
Fumar Cigarrillos
/
Inflamación
/
Neutrófilos
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos