Regulation of cytoplasmic pH in phagocytic cell function and dysfunction.
To ensure effective antimicrobial or tumouricidal function, phagocytic cells must maintain their cytoplasmic pH (pHi) at a level conductive to optimal intracellular enzyme activity. The mechanisms by which neutrophils and macrophages regulate their cytoplasmic pH include bicarbonate-independent ion transport systems, most notably the Na+/H+ exchanger, and bicarbonate-dependent ion transport systems, which can be subdivided into the cation-independent and Na(+)-dependent forms of chloride/bicarbonate exchange. In addition, macrophages have been shown to recover from intracellular acid loading by means of an ATP-dependent proton extrusion mechanism, which has the characteristics of a vacuolar-type H+ ATPase. In the microenvironment typically associated with abscesses, the low extracellular pH and the presence of short chain fatty acid by-products of bacterial metabolism tend to induce cytoplasmic acid loading. In this setting, the ability of the various pHi regulatory mechanisms to protect pHi may be overcome, leading to cytoplasmic acidification. Several investigators have shown that cytoplasmic acidification impairs the ability of neutrophils to migrate in response to chemotactic stimuli, and also impairs their ability to generate a respiratory burst, thus inhibiting the release of toxic oxygen radicals. This may result in the inability of phagocytes to effect complete abscess resolution.
Grinstein
S
S
Division of Cell Biology, Hospital for Sick Children, Toronto, Canada.
Swallow
C J
CJ
Rotstein
O D
OD
D000038:Abscess / Q000276:immunology / Q000378:metabolism; D000136:Acid-Base Equilibrium / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D001639:Bicarbonates; D002352:Carrier Proteins; D002712:Chlorides; D005227:Fatty Acids; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D006180:Proton-Translocating ATPases