Page 328 - Industrial Ventilation Design Guidebook

284 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOG1CAL CONSIDERATIONS

therefore in some instances tissue damage may ensue. NO is produced by an en-
zyme, nitric oxide synthase (NOS) which acts on arginine, transforming it into
citrulline and NO. This enzyme has both inducible and constitutive forms. In-
ducible NOS (iNOS) is expressed in immunological cells, mainly phagocytes
such as macrophages and neutrophiles, and in epithelial cells of the airways as
97 116
well as endothelial cells of the circulatory system, ' Constitutive NOS
(cNOS) is expressed in many cells e.g. neuronal cells. It is characteristic of iNOS
that NO is produced only subsequent to persistent induction of the enzyme.
Upon stimulation, the induction of iNOS (stimulated synthesis of the enzyme
protein) may take several hours, but after this time period, the cell can produce
large amounts of NO. When airway epithelial cells and circulatory endothelial
cells produce NO, they contribute to the control of the tone of the smooth mus-
cle in these systems and thus modify airway resistance and blood pressure. 97
NO production is associated with asthma and airway infections; in both situa-
tions, an increased concentration of NO can be measured in the exhaled air. 96
On the other hand, cNOS is continuously expressed in the cells, and upon
stimulation of the cell, the formation of NO begins immediately. However, the
amounts of NO produced are minute. The nature of NO in cells expressing
cNOS is only to act as a messenger molecule, whereas NO has also other func-
tions in cells expressing iNOS. For example, NO has bacteria and cell killing
97 116 117
properties in immunological cells, such as phagocytes. ' '
Nitric oxide may induce deleterious effects when airway epithelial or im-
munological cells are exposed to mineral particles (asbestos, quartz). These
particles also stimulate cells to produce NO in large quantities, but pulmonary
cells are unable to destroy these particles, and a non-physiologically excess
production of NO results, perhaps causing tissue damage due to a reaction of
118 119
NO with cellular macromolecules. '
Immunological Responses and Sens/t/zot/on
A number of chemical compounds are potent sensitizers that can lead to seri-
ous immunological reactions. Immunotoxicology explores interactions between
chemical compounds and the immune system. Chemicals can amplify, attenuate,
or otherwise modify immunological reactions subsequent to exposure. 120
The basic function of the immunological system is to detect and destroy
foreign material that may be harmful to the organism. Cells that belong to the
immunological system include macrophages, monocytes, granulocytes, and T-
and B-lymphocytes. All cells that belong to the immune system have differenti-
ated from the same stem cell. In harmful immunological reactions, the response
of an organism to an exposure changes. The environmental factor does not act
directly, but alters the reaction of the person exposed. The most important
forms of this kind of immunological reactions are (1) immunosuppression; (2)
uncontrolled cell growth, e.g., leukemia and lymphoma; (3) disturbances of im-
munological defense mechanisms against infectious agents and malignant cells;
(4) allergies; and (5) autoimmunity. Allergies will be dealt with in more detail
later in this chapter. 120

Necrotic and Apoptotic Cell Death
The main types of cellular injury induced by chemical compounds are ne-
crotic and apoptotic (programmed) cell death. Necrosis implies chaotic ending