Effect of different treatments on macrophage differentiation in chronic obstructive pulmonary disease and repeated pulmonary infection
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Published on: October 22, 2019
Run Liu1, Zhidian Wu1, Hang Yu1
1Department of Intensive Care Unit, Second Affiliated Hospital of Hainan Medical College, Haikou City 570311, Hainan Province, China.
Objective:
To observe the differentiation of macrophages in lung tissue and alveolar lavage fluid of mice with severe pulmonary infection and the changes after intervention with ceftriaxone and ulinastatin, and to explore the pathogenesis of severe pulmonary infection under immunosuppressive state and the intervention effect of two drugs.
Methods:
40 male Balb/c mice are randomly divided into normal group, model group, ulinastatin group, and ceftriaxone group with 10 mice in each group. Mice models of acute lung injury with immunodeficiency are established by methylprednisolone and endotoxin, and then treated with ulinastatin and ceftriaxone. Respiratory frequencies of mice in each group are measured at 3 h and 6 h after drug use through trachea, and then the mice are anaesthetized with uratan and killed 6 h after drug use. The number of alveolar macrophages and neutrophils in alveolar lavage fluid is collected and detected, and the pathological changes are observed. The positive expression of CD163 in lung tissue is detected by IHC (immunohistochemistry), and real-time quantitative PCR (Polymerase Chain Reaction) is used to detect the expression of Ml and M2 markers in bronchoalveolar lavage fluid (BALF).
Result:
Compared with the normal group, the mice in the model group breathed shallowly and quickly, occasionally nodded breathing, respiratory distress, and respiratory rate increased. Compared with the model group, the mice in the ulinastatin group and ceftriaxone group breathed slowly, occasionally have shortness of breath, smooth breathing, and slow breathing rate, and the mice in ulinastatin group breathe more smoothly. The number of macrophages and neutrophils in BALF of model group is higher than that of normal group. The number of macrophages and neutrophils in ulinastatin group and ceftriaxone group is lower than that of model group and the difference is statistically significant, and the number of macrophages and neutrophils in ulinastatin group is relatively less than that in model group.
Conclusion:
In the early stage of severe pulmonary infection under immunosuppressive state, the organism is in the CARS (Compensatory Anti-inflammatory Response Syndrome) stage; M1 macrophages had immune paralysis and M2 macrophages are abnormally activated. Compared with ceftriaxone, ulinastatin can alleviate lung injury more effectively and protect the lung of mice with acute lung injury. The protective mechanism of ulinastatin on lung of mice infected with immunocompromised endotoxin may be through inhibiting M1 macrophages and regulating non-specific immune function.
Insights
Ulinastatin and ceftriaxone treatment improved respiratory function and reduced inflammatory cells in immunosuppressed mice with severe pulmonary infection. Ulinastatin demonstrated superior efficacy in alleviating lung injury by modulating macrophage responses.
Area of Science:
- Immunology
- Pulmonology
- Pharmacology
Background:
- Severe pulmonary infections in immunosuppressed individuals present complex challenges.
- Understanding macrophage differentiation and activation is crucial for severe lung injury pathogenesis.
Purpose of the Study:
- To investigate macrophage differentiation in severe pulmonary infection under immunosuppression.
- To evaluate the therapeutic effects of ceftriaxone and ulinastatin on lung injury.
- To explore the underlying mechanisms of drug intervention.
Main Methods:
- Established acute lung injury models in immunosuppressed mice using methylprednisolone and endotoxin.
- Administered ulinastatin and ceftriaxone, monitoring respiratory rates.
- Quantified alveolar macrophages and neutrophils in bronchoalveolar lavage fluid (BALF).
- Assessed CD163 expression and M1/M2 macrophage markers via immunohistochemistry and real-time PCR.
Main Results:
- Model mice exhibited respiratory distress; treatment groups showed improved breathing.
- BALF revealed significantly reduced macrophages and neutrophils in ulinastatin and ceftriaxone groups compared to the model group.
- Ulinastatin group displayed smoother breathing and fewer inflammatory cells than the ceftriaxone group.
Conclusions:
- Severe pulmonary infection in immunosuppression may involve Compensatory Anti-inflammatory Response Syndrome (CARS) with M1 immune paralysis and M2 activation.
- Ulinastatin offers more effective lung protection than ceftriaxone in this model.
- Ulinastatin's protective effect may stem from inhibiting M1 macrophages and regulating non-specific immunity.
