Depletion of pulmonary intravascular macrophages rescues inflammation-induced delayed neutrophil apoptosis in horses.

This investigation studied how reducing the number of a specific type of immune cell (pulmonary intravascular macrophage) in the lungs can affect inflammation and cell death (apoptosis) of another type of immune cell (neutrophil) in horses with a specific type of intestinal damage (ischemia and reperfusion injury).

Study Overview

• The study aimed to understand how reducing pulmonary intravascular macrophages (immune cells located inside blood vessels in the lungs), impacts systemic inflammation and the process of programmed cell death (apoptosis) in neutrophil cells.
• Research was carried out using horses that had undergone a specific type of intestinal damage called intestinal ischemia and reperfusion injury. The experiments included three treatment groups including one control group (sham celiotomy), one group with induced intestinal damage (ischaemia and reperfusion), and a third group that was not only subject to induced intestinal damage but also treated with gadolinium chloride to deplete pulmonary intravascular macrophages.

Results

• After surgery, a delayed apoptosis in neutrophils (white blood cells integral to the body’s immune system that engage in the early phases of inflammation) was observed across all horses. However, this delay was not seen in the group where pulmonary intravascular macrophages (PIMs) were depleted.
• Neutrophils isolated after surgery and cultured for 12 hours in horses with ischemia (insufficient blood supply) and reperfusion (restoration of blood flow) had significantly decreased activity levels of caspase-3, caspase-8, and caspase-9, which are enzymes largely responsible for carrying out apoptosis. In contrast, this decrease in activity was not seen in the horses where PIMs were depleted.
• Blood levels of a pro-inflammatory molecule TNF-α were found to be increased in horses in which PIMs were depleted. It suggests that this upregulation of TNF-α could be the way that the depletion of PIMs counteracted the delay in neutrophil apoptosis caused following surgery.

Conclusion

• The results suggest an intricate interaction between different types of immune cells: the depletion of one type (PIMs) potentially affects the lifespan/turnover of another (neutrophils). This work could potentially be utilized to alleviate inflammation and its adverse effects in a variety of clinical scenarios where similar pathological mechanisms are involved.