Department of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland
Correspondence: Dr. Anne Lardner, Department of Biological Sciences, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland. E-mail: Anne.Lardner{at}dit.ie
The effect of alterations in extracellular pH on cellular and humoral immune function is reviewed. Because acidic pH predominates at inflammatory loci and other sites of immune activity, most studies to date focus on the effect of acidic rather than alkaline pH. Investigations on polymorphonuclear leukocytes demonstrate mainly inhibition of chemotaxis, respiratory activity, and bactericidal capacity at reduced pH. Evidence of impaired lymphocyte cytotoxicity and proliferation at acidic pH is also beginning to emerge. Many of the clinical acidoses are accompanied similarly by immunodeficiency. Studies on macrophages and eosinophils are few and inconclusive. A small number of studies demonstrate acid-induced activation of complement proteins and the alternative complement pathway, plus increased antibody-binding to leukocytes at lowered pH. A differential effect of acidic pH on humoral and cellular immunity may, therefore, exist. Increasing recognition of the significance of extracellular pH in relation to immune function warrants further studies in this presently incomplete but rewarding field.
Key Words: immunity • acidosis • leukocytes • immunodeficiency • humoral • cellular
This article has been cited by other articles:
 |
|
 |
|
  V. Babich, L. Knipe, L. Hewlett, A. Meli, J. Dempster, M. J. Hannah, and T. Carter Differential Effect of Extracellular Acidosis on the Release and Dispersal of Soluble and Membrane Proteins Secreted from the Weibel-Palade Body J. Biol. Chem., May 1, 2009; 284(18): 12459 - 12468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Silva, J. A. Yunes, R. J. Gillies, and R. A. Gatenby The Potential Role of Systemic Buffers in Reducing Intratumoral Extracellular pH and Acid-Mediated Invasion Cancer Res., March 15, 2009; 69(6): 2677 - 2684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Mogi, M. Tobo, H. Tomura, N. Murata, X.-d. He, K. Sato, T. Kimura, T. Ishizuka, T. Sasaki, T. Sato, et al. Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Proinflammatory Cytokine Production in Peritoneal Macrophages J. Immunol., March 1, 2009; 182(5): 3243 - 3251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. V. Bocharov, M. L. Mayzel, P. E. Volynsky, M. V. Goncharuk, Y. S. Ermolyuk, A. A. Schulga, E. O. Artemenko, R. G. Efremov, and A. S. Arseniev Spatial Structure and pH-dependent Conformational Diversity of Dimeric Transmembrane Domain of the Receptor Tyrosine Kinase EphA1 J. Biol. Chem., October 24, 2008; 283(43): 29385 - 29395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Numata and Y. Okada Proton Conductivity through the Human TRPM7 Channel and Its Molecular Determinants J. Biol. Chem., May 30, 2008; 283(22): 15097 - 15103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Westphal, S. Leschner, J. Jablonska, H. Loessner, and S. Weiss Containment of Tumor-Colonizing Bacteria by Host Neutrophils Cancer Res., April 15, 2008; 68(8): 2952 - 2960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Sandoval, J. P. Riquelme, M. D. Carretta, J. L. Hancke, M. A. Hidalgo, and R. A. Burgos Store-operated calcium entry mediates intracellular alkalinization, ERK1/2, and Akt/PKB phosphorylation in bovine neutrophils J. Leukoc. Biol., November 1, 2007; 82(5): 1266 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Cooper, S. Radom-Aizik, C. Schwindt, and F. Zaldivar Jr. Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity J Appl Physiol, August 1, 2007; 103(2): 700 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Fischer, P. Hoffmann, S. Voelkl, N. Meidenbauer, J. Ammer, M. Edinger, E. Gottfried, S. Schwarz, G. Rothe, S. Hoves, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells Blood, May 1, 2007; 109(9): 3812 - 3819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Vitale, B Cambien, B F Karimdjee, R Barthel, P Staccini, C Luci, V Breittmayer, F Anjuere, A Schmid-Alliana, and H Schmid-Antomarchi Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer Gut, March 1, 2007; 56(3): 365 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, D. Zhou, A. G. Vicencio, J. Ryu, J. Xue, A. Kanaan, O. Gavrialov, and G. G. Haddad Effect of carbon dioxide on neonatal mouse lung: a genomic approach J Appl Physiol, December 1, 2006; 101(6): 1556 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Gatenby, E. T. Gawlinski, A. F. Gmitro, B. Kaylor, and R. J. Gillies Acid-mediated tumor invasion: a multidisciplinary study. Cancer Res., May 15, 2006; 66(10): 5216 - 5223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Cairns, I. Papandreou, and N. Denko Overcoming Physiologic Barriers to Cancer Treatment by Molecularly Targeting the Tumor Microenvironment Mol. Cancer Res., February 1, 2006; 4(2): 61 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nareika, L. He, B. A. Game, E. H. Slate, J. J. Sanders, S. D. London, M. F. Lopes-Virella, and Y. Huang Sodium lactate increases LPS-stimulated MMP and cytokine expression in U937 histiocytes by enhancing AP-1 and NF-{kappa}B transcriptional activities Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E534 - E542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. Parks, G. P. Gambill, A. J. Lusis, and J. H. S. Kabarowski Loss of G2A promotes macrophage accumulation in atherosclerotic lesions of low density lipoprotein receptor-deficient mice J. Lipid Res., July 1, 2005; 46(7): 1405 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Lang, P. Dong, E. K. Hosszu, and I. R. Doyle Effect of CO2 on LPS-induced cytokine responses in rat alveolar macrophages Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L96 - L103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ishii, Y. Kihara, and T. Shimizu Identification of T Cell Death-associated Gene 8 (TDAG8) as a Novel Acid Sensing G-protein-coupled Receptor J. Biol. Chem., March 11, 2005; 280(10): 9083 - 9087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Radu, A. Nijagal, J. McLaughlin, L. Wang, and O. N. Witte Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells PNAS, February 1, 2005; 102(5): 1632 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Murakami, T. Yokomizo, T. Okuno, and T. Shimizu G2A Is a Proton-sensing G-protein-coupled Receptor Antagonized by Lysophosphatidylcholine J. Biol. Chem., October 8, 2004; 279(41): 42484 - 42491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Caso, B. A. Garlick, G. A. Casella, D. Sasvary, and P. J. Garlick Acute metabolic acidosis inhibits muscle protein synthesis in rats Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E90 - E96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vermeulen, M. Giordano, A. S. Trevani, C. Sedlik, R. Gamberale, P. Fernandez-Calotti, G. Salamone, S. Raiden, J. Sanjurjo, and J. R. Geffner Acidosis Improves Uptake of Antigens and MHC Class I-Restricted Presentation by Dendritic Cells J. Immunol., March 1, 2004; 172(5): 3196 - 3204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Donovan, A. R. Hippen, D. J. Hurley, and C. C. L. Chase The role of acidogenic diets and {beta}-hydroxybutyate on lymphocyte proliferation and serum antibody response against bovine respiratory viruses in Holstein steers J Anim Sci, December 1, 2003; 81(12): 3088 - 3094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Raghunand, R A Gatenby, and R J Gillies Microenvironmental and cellular consequences of altered blood flow in tumours Br. J. Radiol., December 1, 2003; 76(suppl_1): S11 - S22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Gatenby and E. T. Gawlinski The Glycolytic Phenotype in Carcinogenesis and Tumor Invasion: Insights through Mathematical Models Cancer Res., July 15, 2003; 63(14): 3847 - 3854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Gatenby, E. T. Gawlinski, C. M. Tangen, R. C. Flanigan, and E. D. Crawford The Possible Role of Postoperative Azotemia in Enhanced Survival of Patients with Metastatic Renal Cancer after Cytoreductive Nephrectomy Cancer Res., September 15, 2002; 62(18): 5218 - 5222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.A. Kregenow and E.R. Swenson The lung and carbon dioxide: implications for permissive and therapeutic hypercapnia Eur. Respir. J., July 1, 2002; 20(1): 6 - 11. [Full Text] [PDF]
|
|
|
|
 |
|
 S. SAADI, L. E. WRENSHALL, and J. L. PLATT Regional manifestations and control of the immune system FASEB J, June 1, 2002; 16(8): 849 - 856. [Abstract] [Full Text] [PDF]
|
|
