Contact-dependent, polarized acidification response during neutrophil-epithelial interactions

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Neutrophil (PMN) infiltration during inflammation alters the tissue environment.
• Extracellular acidosis is a common feature of inflammatory responses and influences cellular behavior.

Purpose of the Study:

• To investigate the mechanisms of inflammatory acidification resulting from PMN-intestinal epithelial cell (IEC) interactions.
• To understand the role of PMN transepithelial migration (TEM) in causing local acidosis.

Main Methods:

• Utilized advanced tools to study PMN-IEC interactions and measure extracellular pH.
• Employed physical separation techniques and neutralizing antibodies to modulate PMN-IEC contact and TEM.
• Applied pharmaceutical inhibitors to investigate the involvement of specific enzymes and reactive oxygen species (ROS).

Main Results:

• Inflammatory acidosis during PMN TEM is dependent on the number of PMNs and polarized towards the apical surface.
• Physical separation of PMNs and IECs abolished acidification, while inhibiting PMN TEM enhanced it.
• The acidification response was found to be independent of myeloperoxidase but dependent on ROS generated during PMN TEM.

Conclusions:

• Inflammatory acidosis is a polarized response dependent on PMN-IEC interactions.
• The precise mechanism driving this acidosis requires further elucidation but involves ROS generated during PMN TEM.