extracellular and intracellular pH on immune function cannot be ignored
Posted 08-29-2010 at 07:00 AM by jfh
By now, I'm overwhelmed with all the articles, I've read, with "doctor-speak". It is almost as incomprehensible as Alan Greenspan's Fed-speak. It makes it difficult for someone like me to provide search criteria. I'm pleased with what I've found, and now have to really try to interpret it. These next gleanings came fromhttps://www.jleukbio.org/cgi/content/full/69/4/522
I really encourage you to read it for yourself. I tried not to take anything out of context, but it was hard, slow reading, and most of which I did not understand. I'm exited to have found this information, as it confirms what I've been looking for. I wanted to know what is involved in this relationship between intracellular pH, extracellular pH, and the immune system. The reason it is important to me, is because I had discovered that cecium and sodium bicarbonate do not directly kill the cancer cells. Instead, they weaken them to provide a path for the immune system to do its job.
In this article pHi is intracellular pH, and pHo is extracellular.
OK. Let's start. I'm going to put my comments in brackets within the article and try to make them unique. That's another reason it may be good for you to read the article. It would be without interruption.
------------
The average pH in many tumors is about 0.5 unit lower than normal
surrounding tissues. [It seems minor, just 0.5, but apparently that is very important. That is how the cancer drugs can be selective. Also, cancer tries to hide, by mimicking normal cells.] Therefore, there is a growing awareness among immunologists and oncologists of the potential modulatory role of the prevailing tumor microenvironment on immune cell function. Necrotic foci [dead cells?] are a common feature of solid tumors, probably as a result of, in part, insufficient vascularization and subsequent hypoxia. Hypoxic cells are dependent on glycolysis for their energy needs, and the production of large amounts of lactic is an inevitable consequence of such anaerobic metabolism. [Even probiotic bacteria produce lactic acid.] Lactate accumulation results in a decrease in extracellular pH, which, when combined with hypoxia, results in diminished viability of healthy and cancerous cells. In addition, a drop in pHi from 7.0 to 6.0 results in inhibition of glycolysis with concomitant inhibition of glucose consumption and lactate production [and turns the environment acid]. Therefore, a further consequence of acidic pH isenergy deprivation, and this effect is as applicable to healthy immune cells as it is to cancer cells. Extracellular pH effects are, therefore, becoming increasingly germane to studies of tumor immunology. In an attempt to simulate the three-dimensional milieu of solid tumors, Ratner investigated lymphocyte motility in neutral and acidified extracellular matrix following stimulation with interleukin (IL)-2 in three-dimensional gels. He found increased motility at pH 6.7 compared with pH 7.1, an effect that was abolished in one-dimensional gels. He concluded that the pH effect represents a modification of lymphocyte-matrix interactions and forwarded ambient pH as a microenvironmental factor that can influence lymphocyte motility within tumors. He further speculated on a stimulatory role for weakly acidic tumor microenvironments, and extremely low pH [acid] was toxic to lymphocyte activity. Conversely, a role for extracellular pH in stimulating tumor development through inhibition of immune function is emerging from other in vitro studies. Severin et al. showed diminished cytotoxic activity of human lymphokine-activated killer (LAK) cell activity in acidic pH; Loeffler et al. found a similar depression of murine natural killer (NK) cell activity with lowered pHo.
[Probiotic bacteria also produce acid externally. It is used to kill some bad pathogens. This is good, and we are not trying to kill friendly bacteria.]
...
The lowest pH values are found in those regions where tumor cells are growing adjacent to a basement membrane, causing necrotic foci and promoting tumor invasion. [This gives rise the myth that bad pathogens don't survive in an acid environment. The problem is that there are several pathogens that not only survive in acid, but become aggessive in alkaline, Candida albicans for example.]
...
Ratner proposes that manipulation of intra-tumor pH via systemic acidosis, glucose infusion, or hyperthermia might constitute a useful adjuvant to immunotherapy if lymphocytic infiltration were increased as a result. However, it must be considered that tumor pH may not necessarily decrease in a homogenous manner; low pH may be present in large tumors, and elevated pH may be found in some necrotic areas because of the depletion of glycogen stores in these areas. Also, hypoxia in combination with low-glucose concentration and acidic pHo is capable of killing tumor cells themselves, rendering obsolete the targeted immunotherapy of such cells. In view of the likelihood of variations in pH existing within and around solid tumors, there are likely to be equally heterogenous effects of pH on immune-cell function at the locus of activity, and much research remains to be done in this area. [This says that our bicarbonate protocol may not work on all forms of cancer. And cesium as well.] It should be also considered that cancer cells use glucose at far higher rates than normal cells; thus, it is possible that insufficient glucose may be available for lymphocytes and other immune cells operating within a tumor region, further compromising the overall effectiveness of the immune response. [It is very important to note that cancer cells use glucose at a higher rate than other cells. That's why the SB protocol involves molasses or syrup.] Similarly, the inadequate perfusion of diseased tissues, which are involved in a variety of other pathological conditions such as infarction and resulting necrosis, will result in similar metabolic effects on the surrounding milieu. The effectiveness of the resultant inflammatory processes is just as likely to be compromised by low extracellular pH as are populations of immune cells congregating at the site of tumors. [This paragraph indicates that it is important to bind the molasses with the sodium bicarbonate. This will get it through the stomach acids by neutralizing them. The cancer cell will have a field day with the sugar. Unfortunately opportunistic pathogens will too.]
...
Experimental evidence is emerging gradually for an inhibition of lymphocyte activity when the surrounding pH of tumors is reduced. This may constitute a very significant finding in the context of tumor immunotherapy, and further consideration by clinicians of the effects of the acidic microenvironment of tumors on immune function would appear to be warranted. [You bet. That's how we believe the sodium bicarbonate protocol should work.]
…
Evidently, the inter-relationship between extracellular and intracellular pH on immune function cannot be ignored, especially in light of the myriad findings implicating a role for the Na+/H+ exchanger prior to activation of certain immune activities. The available data strongly suggest that the Na+/H+ exchanger is a sine quanon in generating a rapid intracellular alkalinization prior to differential activation of certain immune activities [Cesium is proven to do this]. It seems reasonable to speculate on a similarly central role for the exchanger in altering pHi in the same direction as pHo. However, the mechanism by which pHi alters in response to changes in pHo warrants investigation. [Remember that Na is sodium and H is hydrogen. The Na+/H+ exchanger is primarily responsible for maintaining the balance of sodium. In this case it is responsible for making the environment alkaline. The Na+/H+ exchanger isoform 1 (NHE1) is primarily responsible for the regulation of intracellular pH (pHi) ]
Pasted from <https://www.jleukbio.org/cgi/content/full/69/4/522>
I really encourage you to read it for yourself. I tried not to take anything out of context, but it was hard, slow reading, and most of which I did not understand. I'm exited to have found this information, as it confirms what I've been looking for. I wanted to know what is involved in this relationship between intracellular pH, extracellular pH, and the immune system. The reason it is important to me, is because I had discovered that cecium and sodium bicarbonate do not directly kill the cancer cells. Instead, they weaken them to provide a path for the immune system to do its job.
In this article pHi is intracellular pH, and pHo is extracellular.
OK. Let's start. I'm going to put my comments in brackets within the article and try to make them unique. That's another reason it may be good for you to read the article. It would be without interruption.
------------
The average pH in many tumors is about 0.5 unit lower than normal
surrounding tissues. [It seems minor, just 0.5, but apparently that is very important. That is how the cancer drugs can be selective. Also, cancer tries to hide, by mimicking normal cells.] Therefore, there is a growing awareness among immunologists and oncologists of the potential modulatory role of the prevailing tumor microenvironment on immune cell function. Necrotic foci [dead cells?] are a common feature of solid tumors, probably as a result of, in part, insufficient vascularization and subsequent hypoxia. Hypoxic cells are dependent on glycolysis for their energy needs, and the production of large amounts of lactic is an inevitable consequence of such anaerobic metabolism. [Even probiotic bacteria produce lactic acid.] Lactate accumulation results in a decrease in extracellular pH, which, when combined with hypoxia, results in diminished viability of healthy and cancerous cells. In addition, a drop in pHi from 7.0 to 6.0 results in inhibition of glycolysis with concomitant inhibition of glucose consumption and lactate production [and turns the environment acid]. Therefore, a further consequence of acidic pH isenergy deprivation, and this effect is as applicable to healthy immune cells as it is to cancer cells. Extracellular pH effects are, therefore, becoming increasingly germane to studies of tumor immunology. In an attempt to simulate the three-dimensional milieu of solid tumors, Ratner investigated lymphocyte motility in neutral and acidified extracellular matrix following stimulation with interleukin (IL)-2 in three-dimensional gels. He found increased motility at pH 6.7 compared with pH 7.1, an effect that was abolished in one-dimensional gels. He concluded that the pH effect represents a modification of lymphocyte-matrix interactions and forwarded ambient pH as a microenvironmental factor that can influence lymphocyte motility within tumors. He further speculated on a stimulatory role for weakly acidic tumor microenvironments, and extremely low pH [acid] was toxic to lymphocyte activity. Conversely, a role for extracellular pH in stimulating tumor development through inhibition of immune function is emerging from other in vitro studies. Severin et al. showed diminished cytotoxic activity of human lymphokine-activated killer (LAK) cell activity in acidic pH; Loeffler et al. found a similar depression of murine natural killer (NK) cell activity with lowered pHo.
[Probiotic bacteria also produce acid externally. It is used to kill some bad pathogens. This is good, and we are not trying to kill friendly bacteria.]
...
The lowest pH values are found in those regions where tumor cells are growing adjacent to a basement membrane, causing necrotic foci and promoting tumor invasion. [This gives rise the myth that bad pathogens don't survive in an acid environment. The problem is that there are several pathogens that not only survive in acid, but become aggessive in alkaline, Candida albicans for example.]
...
Ratner proposes that manipulation of intra-tumor pH via systemic acidosis, glucose infusion, or hyperthermia might constitute a useful adjuvant to immunotherapy if lymphocytic infiltration were increased as a result. However, it must be considered that tumor pH may not necessarily decrease in a homogenous manner; low pH may be present in large tumors, and elevated pH may be found in some necrotic areas because of the depletion of glycogen stores in these areas. Also, hypoxia in combination with low-glucose concentration and acidic pHo is capable of killing tumor cells themselves, rendering obsolete the targeted immunotherapy of such cells. In view of the likelihood of variations in pH existing within and around solid tumors, there are likely to be equally heterogenous effects of pH on immune-cell function at the locus of activity, and much research remains to be done in this area. [This says that our bicarbonate protocol may not work on all forms of cancer. And cesium as well.] It should be also considered that cancer cells use glucose at far higher rates than normal cells; thus, it is possible that insufficient glucose may be available for lymphocytes and other immune cells operating within a tumor region, further compromising the overall effectiveness of the immune response. [It is very important to note that cancer cells use glucose at a higher rate than other cells. That's why the SB protocol involves molasses or syrup.] Similarly, the inadequate perfusion of diseased tissues, which are involved in a variety of other pathological conditions such as infarction and resulting necrosis, will result in similar metabolic effects on the surrounding milieu. The effectiveness of the resultant inflammatory processes is just as likely to be compromised by low extracellular pH as are populations of immune cells congregating at the site of tumors. [This paragraph indicates that it is important to bind the molasses with the sodium bicarbonate. This will get it through the stomach acids by neutralizing them. The cancer cell will have a field day with the sugar. Unfortunately opportunistic pathogens will too.]
...
Experimental evidence is emerging gradually for an inhibition of lymphocyte activity when the surrounding pH of tumors is reduced. This may constitute a very significant finding in the context of tumor immunotherapy, and further consideration by clinicians of the effects of the acidic microenvironment of tumors on immune function would appear to be warranted. [You bet. That's how we believe the sodium bicarbonate protocol should work.]
…
Evidently, the inter-relationship between extracellular and intracellular pH on immune function cannot be ignored, especially in light of the myriad findings implicating a role for the Na+/H+ exchanger prior to activation of certain immune activities. The available data strongly suggest that the Na+/H+ exchanger is a sine quanon in generating a rapid intracellular alkalinization prior to differential activation of certain immune activities [Cesium is proven to do this]. It seems reasonable to speculate on a similarly central role for the exchanger in altering pHi in the same direction as pHo. However, the mechanism by which pHi alters in response to changes in pHo warrants investigation. [Remember that Na is sodium and H is hydrogen. The Na+/H+ exchanger is primarily responsible for maintaining the balance of sodium. In this case it is responsible for making the environment alkaline. The Na+/H+ exchanger isoform 1 (NHE1) is primarily responsible for the regulation of intracellular pH (pHi) ]
Pasted from <https://www.jleukbio.org/cgi/content/full/69/4/522>
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