Acidic pH increases the avidity of FcγR for immune complexes

Abstract

SUMMARYThe interaction of immunoglobulin G (IgG) antibodies with FccR constitutes a critical mechanism through which IgG antibody effector functions are mediated. In the current work we have examined whether human neutrophil FccR exhibit pH dependence in their association with IgG. Binding assays were performed in culture medium adjusted to different pH values. It was found that the binding of either heat-aggregated human IgG (AIgG), soluble immune complexes (sIC) or IgGcoated erythrocytes (IgG-E) was markedly higher at pH 6 e 5 than at pH 7 e 3. This effect was not observed when saturation of FccR was achieved, suggesting that acidic pH increases the avidity of FccR for IC without modifying the total binding capacity. Similar results were observed for the binding of AIgG to either monocytes, natural killer (NK) or K562 cells, suggesting that acidic pH increases the avidity of both, FccRII and FccRIII. Additional experiments were performed to analyse whether the binding of IgG to FccRI also showed pH dependence. To this aim, we employed interferon-c-treated human neutrophils and mouse in¯ammatory macrophages, previously incubated with blocking antibodies directed to FccRII and FccRIII. Acidic pH did not enhance the binding of AIgG nor monomeric IgG under these experimental conditions. Further studies are required to determine whether the enhancement of FccR avidity for IC could be attributed to titration of histidine(s) residues on the Fc fragment of IgG.

Extracellular Acidification Acts as a Key Modulator of Neutrophil Apoptosis and Functions

“…Studies have indicated that extracellular acidification may change the release of inflammatory mediator, and different kinds of acid at specific pH value can cause a different change[ 1 ]. Besides that, extracellular acidification also plays an important role in modulating the function of immune cells, including polymorphonuclear leukocytes, macrophages, and lymphocytes[ 2 , 12 ]. Acid-treated monocytes and macrophages produce more IL-1beta and trigger NLRP3 inflammasome activation[ 13 , 14 ].…”

An Acidic Microenvironment Increases NK Cell Killing of Cryptococcus neoformans and Cryptococcus gattii by Enhancing Perforin Degranulation

“…Although the receptor used by NK cells to recognize Cryptococcus has not been described, NK cells recognize pathogens directly [29] and studies of other receptors suggest that acidic pH can increase ligand binding either by increasing the affinity of receptor and ligand interaction or by increasing the expression of the receptor. For instance, neonatal Fc receptor binds with higher affinity to the Fc portion of IgG at acidic pH, and acidic pH also increases binding of FcγRII (CD32) and FcγRIII (CD16) to immune complexes [30], [31]. Moreover, acidic pH increases expression of CD18 on neutrophils, which is involved in binding to the endothelium [32].…”

The Emerging “Hallmarks” of Metabolic Reprogramming and Immune Evasion: Distinct or Linked?

“…Indeed, Lopez and colleagues (37) showed that acidic pH increases the activity of human immunoglobulin G (IgG) binding to human neutrophils, monocytes, and NK cells. Furthermore, as shown by a number of studies (38)(39)(40)(41)(42)(43), increased activity of the complement system is also observed at lower pH.…”