The pH of Inflammatory Exudates

Extracellular Acidosis Induces Neutrophil Activation by a Mechanism Dependent on Activation of Phosphatidylinositol 3-Kinase/Akt and ERK Pathways

“…Similar observations were made in peritoneal fluid in patients with intra-abdominal infection, as revealed by the analysis of drainage fluid following an emergency laparotomy (4,5) in inflammatory exudates (1,2) as well as in the skin during the course of inflammatory reactions (3). Not only the inflammatory reactions against pathogens but also autoimmune processes such as rheumatoid arthritis and asthma are associated with the development of acidic microenvironments in injured tissues.…”

“…T here is a large body of evidence showing that interstitial acidification is a common feature associated with the course of inflammatory reactions against pathogenic microorganisms in peripheral tissues, where extracellular pH values as low as 5.5-7.0 have been found (1)(2)(3)(4)(5). Similar observations were made in peritoneal fluid in patients with intra-abdominal infection, as revealed by the analysis of drainage fluid following an emergency laparotomy (4,5) in inflammatory exudates (1,2) as well as in the skin during the course of inflammatory reactions (3).…”

Acidosis Improves Uptake of Antigens and MHC Class I-Restricted Presentation by Dendritic Cells

“…Given the critical role of DCs in the induction of immunity, and considering that many inflammatory responses against infectious agents are associated to the development of acidic microenvironments in peripheral tissues (1)(2)(3)(4)(5)(6)(7), it is surprising that no previous work has analyzed the impact of acidosis on DC physiology. This point appears to be relevant not only in anti-infectious immunity, but also in antitumor immunity because acidic regions with values of pH ranging from 5.8 to 7.4 have been described within the solid tumors (8 -15).…”

“…There is a long line of observations, consisting especially of measurements of titratable acidity, which indicate that the inflammatory area is markedly acidic whether the initial irritant be a chemical substance, an allergic reaction, a microbial toxin, or the proliferation of a microorganism (1)(2)(3)(4)(5)(6)(7). Measurements of pH achieved in peritoneal fluid during or after abdominal surgery in infected patients, as well as in situ in peripheral tissues during the development of inflammatory response against many pathogens, have shown extracellular pH values as low as 5.5-7.0 (1, 2, 5, 6).…”

“…They give raise to circulating precursors that home to tissues, in which they reside as immature cells and serve a sentinel function awaiting signals that indicate local infection or inflammation (24 -27). Because immature DCs pick up and process Ags in peripheral tissues (25,27), and considering that the development of many inflammatory processes as well as the growth of different tumors result in the development of acidic microenvironments in peripheral tissues (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), in this study we examined the impact of extracellular acidosis on the function of immature DCs. Our observations indicate that extracellular acidosis improves internalization of Ags, increases the expression of cell surface proteins involved in Ag presentation, promotes an efficient MHC class I-restricted presentation of peptides from exogenous Ags, and also increases the ability of Ag-primed DCs to induce both specific CD8 ϩ CTL responses and specific Ab responses in vivo.…”