ALLERGIC AIRWAY RESPONSES IN P-SELECTIN-DEFICIENT MICE
P-selectin is an adhesion receptor involved in the recruitment of
eosinophils and lymphocytes in a variety of inflammatory conditions,
and it may play an important role in allergen-induced changes in airway
responsiveness. De Sanctis and colleagues (p. 681) sensitized
Pselectin-deficient and wild-type mice to ovalbumin (OVA). Both
groups were then challenged with either OVA to elicit an allergic
response or with phosphate-buffered saline (PBS). Changes in airway
responsiveness to a methacholine challenge were then compared between
the OVA-challenged and the PBS control groups. The allergic response to
OVA challenge, as assessed by the production of immunoglobulin E, was
similar between P-selectin-deficient and wild-type mice. However, the
airway hyperresponsiveness induced by OVA challenge in the wild-type
mice was greatly attenuated in the P-selectin-deficient mice. The
authors conclude that P-selectin plays an important role in OVA-induced
airway hyperresponsiveness via the promotion of airway inflammation.
The paper is discussed in an Invited Editorial by Moqbel (p. 679).
OZONE EXPOSURE INDUCES A PULMONARY HEAT-SHOCK PROTEIN IN GUINEA PIGS
Su and Gordon (p. 707) exposed guinea pigs to ozone for 6 h and killed
them up to 72 h later. Proteins from lavage cells and lung tissue were
characterized by immunoblotting with 72-kDa and 73/72-kDa heat-shock
protein (HSP) monoclonal antibodies. Although 73-kDa HSP was not
affected, 72-kDa HSP was significantly increased in both lavage cells
and lung tissue of animals exposed to 0.4 and 0.66 parts/million of
ozone. This induction of HSPs by ozone may provide clues to the
development of ozone tolerance in humans and animals.
NOVEL MEASUREMENTS OF AIRWAY SURFACE LIQUID THICKNESS
The thickness of airway surface liquid (ASL) in the tracheae and large
bronchi of mammals has been difficult to measure. A recent theoretical
analysis (J. G. Widdicombe. J. Appl.
Physiol. 82: 3-12, 1997) described a new approach
to assessing this thickness by combining measurements of clearance and
permeability of a labeled hydrophilic tracer introduced into the airway
lumen. Duneclift et al. (p. 761) applied this technique to estimate ASL
thickness in excised tracheae of ferrets and rabbits. The results give
values of 40-50 µm for both species, in good agreement with
estimates from two other approaches applied to the same airways.
THYROTROPIN-RELEASING HORMONE AS A RESPIRATORY STIMULANT
The retrotrapezoid nucleus (RTN), a recently described and now
intensively investigated structure near the ventral surface of the
brain stem, plays an important role in the control of breathing in
mammals. Recent studies suggest that it is a key site related to
central chemoreception. Cream et al. (p. 792) demonstrate that the
peptide thyrotropin-releasing hormone (TRH), a known respiratory stimulant, produces long-lasting increases in phrenic nerve activity and in blood pressure when locally applied to RTN in rats. Because TRH
also excites respiratory neurons at other sites, the authors hypothesize that the RTN may participate in coordinating
(cardio)pulmonary responses to stress.
AEROSOL MIXING BY CONVECTIVE STRETCHING AND FOLDING
Aerosol mixing and deposition in the lung periphery cannot be explained
by classic transport mechanisms, such as streamline crossing, inertial
impaction, and gravitational sedimentation. Butler and Tsuda (p. 800)
showed complex flow patterns associated with stretch and fold
convection in small airways of isolated rat lungs. A theoretical
analysis of the interaction between this type of convection and
diffusion was used to quantify the state of mixing. This interaction
resulted in shorter times for aerosol mixing than those predicted by
classic mechanisms. A method using the entropy of aerosol distribution
is proposed to quantify convective mixing.
HYPONATREMIA IN EXERCISING SLED DOGS
Hinchcliff et al. (p. 824) investigated the mechanism of
exercise-associated hyponatremia in Alaskan sled dogs before and after
a 490-km race and in fit dogs that did not run. Water turnover was
significantly greater in the exercise group, and serum sodium concentration fell significantly during the race. Plasma arginine vasopressin decreased, and aldosterone and renin activity increased during the race. Urine osmolality was unchanged, but urine sodium, potassium, and chloride concentrations fell significantly, and urine
urea concentration increased. Thus exercise-induced hyponatremia in a
nonsweating species was associated with increased water turnover and
renal sodium conservation with maintained high urine osmolality. Hyponatremia was speculated to result from urinary loss and inadequate intake of sodium during the race.
IMPORTANCE OF MACROPHAGES IN NATURAL KILLER CELL RESPONSE TO
EXERCISE
There is increasing evidence that exercise alters immune function.
Blank et al. (p. 845) examined the effects of moderate-intensity endurance training in mice on the natural killer (NK) cell cytolytic activity of splenocytes. In cells enriched for the
NK1.1+ surface antigen, training
reduced NK cell cytolytic activity by 20%. However, when macrophages
remained in the in vitro cytolytic activity assay, no training effect
was detected. These findings support the hypothesis that macrophages
may contribute an important modulating influence on the activity of NK
cells in endurance-trained individuals.
PASSIVE MECHANICS OF THE VELOPHARYNX IN PATIENTS WITH OBSTRUCTIVE
SLEEP APNEA
Because the velopharynx is a highly compliant segment of the upper
airway, it is susceptible to partial or complete dynamic collapse
during inspiration, and the three variables, i.e., inspiratory airflow
(
I), driving
pressure across the velopharynx (
P), and velopharyngeal
cross-sectional area
(AVP), are
mutually interdependent. Isono et al. (p. 851) measured these variables
over a range of distending pressures in sleeping patients with
obstructive sleep apnea. Upper airway muscle activity was abolished by
the use of continuous positive pressure applied at the nose. The
results could be described by an equation for
I in terms of
P and AVP. During inspiration with flow limitation,
AVP decreased
progressively, thus raising velopharyngeal impedance and
counterbalancing the increase in
P.
GLUT-4 AND MUSCLE GLYCOGEN RESTITUTION AFTER EXERCISE
Exercise training increases muscle GLUT-4 and hexokinase contents as
well as insulin sensitivity measured under standard conditions. Hickner
and associates (p. 897) have demonstrated positive correlations among
several measures of glucose disposal and muscle glycogen restitution
after exercise. Comparing trained cyclists with untrained control
subjects, the authors measured muscle GLUT-4 content, glycogen synthase
in the active I form, and rate of glycogen repletion after a
combination of prolonged and sprint exercises to
exhaustion. Because circulating insulin and C-peptide
levels were lower in the trained cyclists than in controls, the
investigators conclude that endurance training results in increased
intrinsic ability of muscle to restore glycogen after exercise.