Objective: To study the effects of anti-nerve growth factor (NGF) antibody on the level of autophagy in lung tissue antigen presenting cells in a mouse model of asthma.
Methods: The 24 BALB/c mice aged 6 weeks were divided into control group (PBS sensitization, PBS challenge) , asthma group [ovalbumin (OVA) sensitization, OVA challenge] and anti-NGF group (OVA sensitization, OVA challenge) using the random number table, 8 mice in each group. Sensitization was carried out by intraperitoneal injection method while challenge by aerosol inhalation. The anti-NGF group received intraperitoneal injection of anti-NGF antibody for intervention 30 min before the atomization, while the control group and asthma group received intraperitoneal injection of PBS 30 min before the atomization. The lung tissue and serum were harvested 24 h after the last sensitization. Immunoelectron microscopy was used to observe the level of autophagy in mouse airway dendritic cells. Western blot assay was used to detect the autophagy marker molecule MHP1 LC3-II level in lung tissue. ELISA was used to detect the serum levels of IL-4, INF-γ and NGF. Immunohistochemical technique was used to detect the expression levels of costimulatory molecules CD₈₀, CD₈₆ and CD₄₀, and the major histocompatibility complex class II molecule (MHC-II) on dendritic cells of lung tissue.
Results: The level of autophagy in lung tissue was lower in anti-NGF group (0.28 ± 0.07) than in asthma group (0.46 ± 0.10) but higher than in control group (0.17 ± 0.08) (F = 15.571, P < 0.05) ; and Pairwise comparison showed that all the intergroup differences were statistically significant (all P values<0.05) . The serum NGF concentration was lower in anti-NGF group [(0.65 ± 0.04) µg/L] than in asthma group [(0.75 ± 0.10) µg/L] but still higher than the control group [(0.52 ± 0.05) µg/L] (F = 61.972, P < 0.05); and Pairwise comparison showed that all the intergroup differences were statistically significant (all P values<0.05) . Both the costimulatory molecules CD₈₀, CD₈₆ and CD₄₀ and the MHC-II on antigen presenting cells of lung tissue were significantly lower in anti-NGF group than in asthma group. Anti-NGF group had lower serum IL-4 but higher IFN-γ level than asthma group.
Conclusions: Anti-NGF antibody attenuates Th2-dominant airway inflammation in this mouse model of asthma by down-regulating the level of autophagy in lung tissue to inhibit the antigen-presenting cell functions.