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. 2006 Nov 7:3:14.
doi: 10.1186/1743-8977-3-14.

Effects of nitric oxide synthase inhibitor omega-nitro-L-arginine methyl ester, on silica-induced inflammatory reaction and apoptosis

He Wang  1 , James Leigh
Affiliations

Effects of nitric oxide synthase inhibitor omega-nitro-L-arginine methyl ester, on silica-induced inflammatory reaction and apoptosis

He Wang et al. Part Fibre Toxicol. .

Abstract

Background: Although nitric oxide is overproduced by macrophages and neutrophils after exposure to silica, its role in silica-induced inflammatory reaction and apoptosis needs further clarification. In this study, rats were intratracheally instilled with either silica suspension or saline to examine inflammatory reactions and intraperitoneally injected with omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthases, or saline to examine the possible role of nitric oxide production in the reaction.

Results: Results showed that silica instillation induced a strong inflammatory reaction indicated by increased total cell number, number of neutrophils, protein concentration and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF). There were no significant differences in these indices between silica-instilled groups with and without L-NAME injection (p > 0.05) except LDH level. The results also showed that apoptotic leucocytes were identified in BALF cells of silica-instilled groups whereas no significant difference was found between silica-instilled groups with and without L-NAME injection in the apoptotic reaction (p > 0.05). Silica instillation significantly increased the level of BALF nitrite/nitrate and L-NAME injection reduced this increase.

Conclusion: Intratracheal instillation of silica caused an obvious inflammatory reaction and leucocyte apoptosis, but these reactions were not influenced by intraperitoneal injection of L-NAME and reduced production of NO. This supports the possibility that silica-induced lung inflammation and BALF cell apoptosis are via NO-independent mechanisms.

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Figures

Figure 1
Figure 1
Total cell number in bronchoalveolar lavage fluid of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME). QL = silica (quartz) + L-NAME; QS = silica + saline; SL = saline + L-NAME; SS = saline + saline (These abbreviations also apply to subsequent figures) (mean + se).
Figure 2
Figure 2
Percentage of neutrophils in BALF cells of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 3
Figure 3
Percentage of macrophages in BALF cells of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 4
Figure 4
Protein concentration in bronchoalveolar lavage fluid of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 5
Figure 5
Lung weight of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 6
Figure 6
LDH activity in bronchoalveolar lavage fluid of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups. * * There is a statistically significant difference in comparison with saline-injected group.
Figure 7
Figure 7
Proportion of apoptotic leucocytes in BALF leucocytes of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 8
Figure 8
Percentage of apoptotic neutrophils in BALF neutrophils of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 9
Figure 9
Proportion of pulmonary alveolar macrophages with engulfed apoptotic neutrophils in BALF macrophages of rats after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). * There is a statistically significant difference in comparison with control groups.
Figure 10
Figure 10
(a) Concentration of NO2-/NO3- (μM) in BALF of rats 2 weeks after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). ** There is a statistically significant difference in comparison with control groups. * There is a statistically significant difference in comparison with instillation of silica and injection of saline group. (b) Concentration of NO2-/NO3- (μM) in BALF of rats 4 weeks after intratracheal instillation of silica or saline and intraperitoneal injection of saline or ω-nitro-L-arginine methyl ester (L-NAME) (mean + se). ** There is a statistically significant difference in comparison with control group. * There is a statistically significant difference in comparison with instillation of silica and injection of saline group.
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