Exudative neutrophils show impaired pH regulation compared with circulating neutrophils

D J Hackam1, S Grinstein, A Nathens

  • 1Department of Surgery, Toronto Hospital, University of Toronto, Ontario.

Abstract

Insights

Neutrophils (PMN) migrating to inflammation sites show impaired cytosolic pH regulation, impacting their function. This dysfunction in pH balance may hinder infection resolution.

Area of Science:

  • Immunology
  • Cellular Physiology

Background:

  • Neutrophil transmigration is crucial for inflammatory response.
  • Cytosolic pH (pHi) regulation is vital for cellular function.

Purpose of the Study:

  • To investigate how neutrophil (PMN) transmigration affects cytosolic pH (pHi) regulation at inflammatory sites.

Main Methods:

  • Exudative PMNs were collected from rats with endotoxin-induced lung injury.
  • Circulating PMNs were purified via density-gradient centrifugation.
  • Single-cell fluorescence imaging with biscarboxyethyl-carboxyfluorescein measured pHi.

Main Results:

  • Exudative PMNs exhibited impaired pHi recovery from acid loads compared to circulating PMNs.
  • Under extracellular acidosis, exudative PMNs showed poorer pHi homeostasis and reduced superoxide production.
  • Sodium-proton exchanger inhibition partially corrected pHi recovery differences.

Conclusions:

  • Impaired pHi regulation in exudative neutrophils may contribute to cellular dysfunction.
  • This dysfunction could impede the resolution of inflammation and infection.