Environmental Pollutants and the Immune System
OR "It's Not Nice to Fool Mother Nature"
By David H. Sherr PhD
Department of Environmental Health, Boston University School of Public Health
This article is the first in the series "From Research to Real Life" that GBPSR presents in conjunction with the Boston University Superfund Basic Research Program (BUSBRP).
We hope this information encourages you to become more involved in PSR programs or other activities that address preventing toxic exposures that may jeopardize public health.
In evolution, surprisingly little is left to chance. Biologic systems, whether composed of millions of liver cells working in concert to detoxify the blood, or white blood cells attempting to defend against foreign microbe invasion, are "designed" with controls, regulators, checks, and balances. The selective value of such biologic oversight is the evolution of systems that, despite their complexity, tend not to fail.
For example, all animal cells are equipped with dozens of proteins that regulate how frequently a cell divides. Should some of the regulatory machinery become defective, cells generally invoke a genetically encoded suicide program.
It actually takes several events to impair both growth regulation and activation of the cell death program, and in that rare instance, a cancer is formed. Even so, most tumors go undetected because they are eliminated quickly by the sentinel immune system.
It's when the balance between growth and death is tipped in the direction of growth, and the immune system is impaired that bad things happen. Our laboratory studies show how several environmental pollutants do exactly that.
Immune System Protects Health
The immune system is responsible for defending its host against invading bacteria, viruses, fungi, and, as noted above, newly formed cancers. Defense against bacteria and fungi is assumed primarily by a system of interacting white blood cells known as the B lymphocyte arm of the immune system. B lymphocytes mass produce proteins (antibodies) which bind to and kill microbes. Each B cell is capable of producing antibody of only one given specificity. The development of millions of B lymphocytes expressing millions of specificities insures that the immune system has the potential to respond to millions of different foreign insults.
The B cells must "learn" their specificities early in their development, must grow enough to constitute the host with a significant mass of B cells of every given specificity, and must learn not to respond to self components. B cells that fail to learn the difference between "self" and "foreign" components are forced to activate the suicide program, sparing the host from autoimmune disease. This education occurs continually in the bone marrow, where all eight kinds of blood cells are produced.
The failure of immature B lymphocytes to learn these lessons results either in an inadequate immune response to foreign microbes, leaving the host susceptible to infection, or to an inappropriate autoimmune reaction to host tissue. Unfortunately, just like babies and young children, bone marrow B cells are more sensitive to environmental pollutants then their more mature counterparts.
Pollutants Can Disrupt Immune System
Our laboratory has shown that two classes of common pollutants, aromatic hydrocarbons and phthalates, disrupt B cell education. Hydrocarbons are ubiquitous and are produced every time something organic is burned - from fossil fuels in our cars and coal in our power plants, to charcoal broiled steaks. Phthalates, which leach from hundreds of common products containing plasticizers (e.g. medical tubing, plastic bags, cosmetics), can also be found throughout our environment.
The effects of these chemicals on immature B lymphocytes are dramatic. Hydrocarbons, many of which are carcinogenic, prematurely induce bone marrow B cells to initiate the cell death program. Notably, the doses of hydrocarbons required to suppress B cell development are significantly lower than those required to induce cancers. Consequently, estimates of hydrocarbon exposure risks, which generally involve cancer as an endpoint, may underestimate the dangers of pollutant exposure.
It has been demonstrated that phthalates similarly induce programmed cell death. Indeed, the strength of the death signal delivered by phthalate-like chemicals is the strongest suicide signal our laboratory has ever seen. At low doses, phthalates spare B cells from the death program but induce them to cease growth.
Research Focusing on Mechanisms of Disruption
A key goal in our laboratory is to define, on a molecular level, how these chemicals invoke aberrant cellular responses. Both hydrocarbons and phthalates are recognized by distinct cellular protein receptors that transmit signals to cell nuclei wherein reside genetic programs for cell suicide and growth regulation. This begs the question of what these receptors evolved to do in the first place; certainly they haven't evolved to recognize by-products of human industry.
We must conclude then that activation of these receptors by environmental chemicals is an unwise practice, one that clearly was not part of mother nature's evolutionary plan. And we all know that it's not nice to fool mother nature.
Dr. Sherr holds joint appointments in the Department of Environmental Health and in the Department of Pathology and Laboratory Medicine in the Boston University School of Medicine. He also heads the Sherr laboratory research facility.