Health Effects of Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 577

TABLE 23.4
Summary of Immunological Mechanisms for the Clearance of Intact Biological Particles a
Innate immune (nonspeciic) response b
Cytokines/chemokines (pro-inlammatory, anti-inlammatory, activating)
Speciic ligands (e.g., CD14 receptor for endotoxin)
Natural antibodies
Microbe-speciic antibodies found in healthy people in the absence of overt infection
Opsonin-independent phagocytosis
Engulfment of biological particles in the absence of speciic antibodies by macrophages and polymorphonuclear
leukocytes
Acute-phase proteins
Speciic immune responses c
Pathogen-speciic antibodies
Cell-mediated immunity
Complement system
System of more than 30 proteins that acts with or without antibody to initiate inlammatory reactions and to kill viable
biological particles
a This table is created from material in Chapters 4-9 of Ref. [275].
b The innate immune system is the part of the immune response that does not require speciic response to pathogens and
is the irst response to pathogens not previously encountered by a host. The innate immune response is rapid compared
to the delayed response of speciic immunity.
c Speciic immune responses are classiied broadly as those related to antibodies and those related to direct cellular
effects. This system is activated by a complex process of recognition, processing, and presentation of foreign antigens,
which leads to activation of speciic limbs of the speciic immune response system.
achieved between 10 and 20 min [30]. Once in the bloodstream, free particles and particles con-
tained in macrophages can be deposited in any extrapulmonary organ. Particles that are ingested
by macrophages may dissolve in certain environments within the cells (e.g., the acidic environment
of phagolysosomes).
Soluble particles are removed by absorption. Absorption is described as a two-stage process:
dissolution (dissociation of particles into material that can be absorbed) and uptake of the material.
Each of these steps is time dependent, for which surface properties, chemical structure, and surface-
to-volume ratio are important determinants.
Whether a particle is cleared or retained for some period of time is dependent on the physi-
cochemical properties of the particle, site of deposition, presence of underlying diseases, and
occurrence of tobacco smoking [22]. Explanations for the increased deposition and possible reten-
tion in persons with underlying lung disease are not well understood but, in part, may be related
both to structural alterations and functional changes in the lung (e.g., altered epithelial perme-
ability) [31,32]. In healthy individuals, poorly soluble particles are estimated to be cleared over
a 2.5-20 h period. Persons with chronic lung disease and certain infections (e.g., inluenza) may
have impaired clearance of particles. The effect of physical activity on deposition and clearance is
unresolved. However, a recent study that used a mouthpiece exposure system showed that deposi-
tion of ultraine carbon particles (count median diameter = 26 nm, GSD = 1.6) was increased in 12
healthy subjects who exercised moderately, with a 4.5-fold increase in the total number of depos-
ited particles [33].
Figure 23.13 illustrates the effects of duration of exposure on retention of particles for three par-
ticle modes and total lung burden as a function of age for a speciic aerosol composition. Of interest
for health considerations is the different time course and magnitude of lung burden for the three