Acute Psychological Stress and Exercise and Changes in Peripheral Leukocyte

Adhesion Molecule Expression and Density

MARION U. GOEBEL, MSC, AND PAUL J. MILLS, PHD
Objective: This study examined the effects of acute psychological stress and exhaustive exercise on the expression
and density of adhesion molecules (L-selectin, lymphocyte function antigen-1 [LFA-1], and intracellular adhesion
molecule-1 [ICAM-1]) on monocytes, granulocytes, and lymphocytes. Methods: Forty-five healthy volunteers
performed a 15-minute public speaking task and a 15- to 18-minute bicycle ergometer challenge. Results: In general,
both the exercise and speaking tasks led to increases in the number of circulating leukocytes and lymphocyte
subsets. The density of L-selectin (CD62L) on mixed lymphocytes and T lymphocytes was decreased in response to
exercise (p values ⬍ .001). Both stressors led to an increased density of LFA-1 (CD11a) on mixed lymphocytes (p
values ⬍ .01), whereas CD11a density on monocytes and granulocytes remained unchanged. ICAM-1 (CD54) density
was unaffected, but the number of lymphocytes, monocytes, and granulocytes expressing CD54 increased in the
circulation on both stressors. Conclusions: The data indicate that both psychological stress and exercise have
significant effects on cellular expression of adhesion molecules on circulating leukocytes. Given the crucial role that
adhesion molecules on circulating cells play in inflammation and disease, these findings may have clinical
relevance in sympathetic nervous system–induced immune activation. Key words: CD62L, CD11a, CD54, adhesion
molecules, stress, exercise.

vating signals, CD11a is upregulated to the high-affin-

CD62L ⫽ L-selectin; CD11a ⫽ LFA-1; CD54 ⫽ ICAM-1;
ICAM ⫽ intercellular adhesion molecule; LFA ⫽ lym-
phocyte function-associated antigen; NK ⫽ natural
killer (cell); PE ⫽ phycoerythrin; SNS ⫽ sympathetic
nervous system; VO2max ⫽ maximum oxygen con-
sumption.
Leukocytosis, an increase of leukocytes in the cir-
culation in response to acute psychological stress or
short-term intensive exercise, is a well-documented
phenomenon (1). Yet the underlying mechanism of
altered lymphocyte trafficking on acute activation of
the SNS has not been fully revealed. Previous studies
in this field have focused on the relation among cat-
echolamines, adrenoreceptor mechanisms, and altered
leukocyte trafficking (2– 4). There is growing evidence
that cellular adhesion molecules are also altered after
acute activation of the SNS and might therefore con-
tribute to stress-induced leukocytosis (5).
Adhesion molecules expressed on the cell surface of
both the leukocyte and the endothelial wall have a
pivotal role in leukocyte trafficking (6, 7). CD62L is
expressed on most circulating leukocytes and medi-
ates leukocyte rolling and regulates the homing of
naive lymphocytes to secondary lymphoid tissues (8).
CD11a is expressed on all leukocytes and exists in
either a low- or high-affinity state. In response to acti-
From the Department of Psychiatry (M.U.G, P.J.M.), University of
California, San Diego, La Jolla, CA; and the Department of Medical
Psychology (M.U.G.), University of Essen, Essen, Germany.
Address reprint requests to: Marion U. Goebel, MSc, Department
of Medical Psychology, University of Essen, Hufelandstrasse 55,
D-45122 Essen, Germany. Email: marion.goebel@uni-essen.de
Received June 21, 1999; revision received March 10, 2000.
ity state, a process that likely involves aggregation on
the cell surface and changes in conformation (9). Once
activated, CD11a binds tightly to its ligands (ICAM-1,
ICAM-2, or ICAM-3) on the endothelium, and this is
generally followed by leukocyte transendothelial mi-
gration (9).
Kurokawa et al. (10) reported a greater increase of
CD8⫹ lymphocytes with high expression of CD11a
(CD8⫹CD11ahigh⫹) compared with low expression of
CD11a (CD8⫹CD11alow⫹), as well as a preferential in-
crease of CD62L⫺ but not CD62L⫹ T cells after inten-
sive exercise. More recent studies confirm that a cer-
tain pattern of adhesion molecule expression is
involved in the differential mobilization of lympho-
cyte subsets on exercise (11, 12). Moreover, prior treat-
ment with the nonselective ␤-blocker propranolol at-
tenuates the increase of CD62L⫺ T lymphocytes on
exercise, showing the coregulatory function of ␤2-ad-
renergic mechanisms in the redistribution of CD62L⫺
T cells (13).
Still it is unclear whether these findings are due to
a loss (shedding) of CD62L, an influx of CD62L⫺ cells,
an efflux of CD62L⫹ cells, or a combination of these
factors. Studies examining soluble adhesion molecules
such as E-selectin (CD62E) and ICAM-1 support the
possibility of shedding on exercise (14, 15). On the
other hand, activated lymphocytes and a subpopula-
tion of memory T cells express lower levels of CD62L,
suggesting a distinct recruitment of these cells after
activation of the SNS (16, 17). In addition, exercise has
been found to preferentially mobilize cells with higher
CD11a expression (18).
Regarding the question of the origins of the invading
cells, it is likely that during exercise leukocytes are
mobilized from the marginal pools of blood vessels
(19). Catecholamines probably reduce the adhesive-

664 Psychosomatic Medicine 62:664 – 670 (2000)

0033-3174/00/6205-0664
Copyright © 2000 by the American Psychosomatic Society
PSYCHOLOGICAL STRESS, EXERCISE, AND ADHESION
ness, and together with an increase in blood velocity,
leukocytes are detached into circulation (1, 19). Also,
the spleen is thought to promote the leukocytosis be-
cause Nielsen (2) demonstrated that the spleen pro-
vides two-thirds of invading lymphocytes during
exercise.
In contrast to exercise, little attention has been paid
to the effects of acute psychological stress on adhesion
molecules (20). Lymphocyte redistribution after an
acute psychological stressor generally seems to follow
a similar mechanism as exercise, with accompanying
increases in epinephrine and norepinephrine (21). Us-
ing the chronic stress model of Alzheimer’s caregivers,
we recently observed lower CD62L expression on T
lymphocytes of stressed caregivers as compared with
control subjects (22). However, the physiological
meaning of downregulation of CD62L is unclear. Al-
though we know little about the changes of adhesion
molecule expression and its impact on leukocyte traf-
ficking in the different contexts of acute and chronic
stress (23, 24), the clinical application for inflamma-
tory diseases or transplantation is apparent (25, 26).
Interestingly, altered adhesion molecule expression is
thought to have an impact during myocardial infarc-
tion (27).
Few, if any, studies have investigated and compared
the differential effects of acute psychological stress
and exercise on the expression of adhesion molecules.
Therefore, we examined and compared and contrasted
the effects of a standardized speaking task and an
exercise task on adhesion molecules. To facilitate com-
parison of our data to data from existing exercise stud-
ies, we studied L-selectin, ICAM-1, and LFA-1. We
quantified adhesion molecule expression and density
on lymphocytes, monocytes, and granulocytes.
METHODS
Subjects
Forty-five healthy volunteers (mean age ⫽ 36 years, SD ⫽ 7 years)
were studied after they provided written informed consent. All
subjects provided a history and underwent physical examination
(performed by a physician) and were identified as healthy. All
underwent electrocardiography to ensure that there were no cardiac
abnormalities before participation, and only those with normal re-
sults on their electrocardiogram were studied. Volunteers were re-
cruited from the local community and were paid for their participa-
tion. The protocol was approved by the institutional review board of
the University of California, San Diego.
Procedures
All subjects were studied at the UCSD Medical Center General
Clinical Research Center between 8:15 AM and 12:00 PM. Subjects
refrained from consuming caffeinated beverages and smoking for 12
hours before study. On arrival at the laboratory, subjects were
Psychosomatic Medicine 62:664 – 670 (2000)
seated, a 19-gauge catheter was inserted into a forearm vein, and
then they rested for 30 minutes. Starting at 9:00 AM, in a fixed order,
volunteers performed a 15-minute speaking task and a 15- to 18-
minute bicycle ergometer exercise. There was a 60-minute period
between completion of each task and the start (baseline) of the next
task. The speaking task consisted of two back-to-back speeches.
While seated, the subject prepared (3 minutes/speech) and then
presented a speech (3 minutes/speech) on a hypothetical situation.
The total time of the speaking task, including the 6 minutes of
preparation, the 6 minutes of presentation, and instruction, was
approximately 15 minutes. Subjects were told that the speech would
be evaluated and rated by experts. The two speeches involved de-
fending oneself from being falsely accused of shoplifting and a
confrontation with an unscrupulous car dealer. If subjects stopped
speaking before the time was up, they were reminded to continue
talking by reiterating and summarizing their points (28).
For the exercise task, subjects were informed that the exercise
itself would last 15 to 18 minutes, beginning with a series of
3-minute stages marked by increasing resistance and thus greater
effort on their part. They were told that the peak level of effort would
be challenging and that once that peak had been established the
workload would actually be slightly reduced for the remainder of
the exercise period. They were informed of warning signs of excess
exertion (eg, faintness, shortness of breath, dizziness, and muscle
cramps) and that although such complications were not expected,
they should inform the investigator immediately if any occurred.
Subjects were instructed to begin pedaling and to achieve and main-
tain a pedal rate of 70 rpm as indicated on the ergometer display
panel in their view. VO2max was estimated using heart rate, and
workload was adjusted so that the exercise was completed at a level
comparable to 75% of estimated VO2max for each subject. After the
test, wheel resistance was removed, and subjects continued to pedal
freely against no resistance for 5 minutes (cooldown period).
Leukocyte Subsets
Whole blood was sampled before, immediately after, and 15
minutes after each challenge. Blood was preserved with ethyl-
enediaminetetraacetic acid and maintained at room temperature
(23°C). Complete blood count was analyzed by using a Coulter STKS
CBC Counter. Flow cytometry (FACSCalibur, Becton Dickinson, San
Jose, CA) using CellQuest software was used to quantify lympho-
cyte, monocyte, and granulocyte populations and adhesion mole-
cules (29). Blood was processed within 3 hours of collection and was
stained with monoclonal antibodies conjugated to various fluoro-
chromes. The lysing reagent was FACS Brand Lysing Solution (Bec-
ton-Dickinson), which results in simultaneous lysis of red blood
cells and partial fixation of leukocytes. Positive four-color staining
was used with monoclonal antibodies conjugated to either fluores-
cein isothiocyanate, PE, peridinin chlorophyll protein, or allophy-
cocyanin (Becton-Dickinson and PharMingen, San Jose, CA). Fluo-
rescence compensation was performed using CaliBRITE beads
(Becton-Dickinson) and FACSComp software. Optimal amounts of
antibodies were used and 8000 to 15,000 events were analyzed per
tube. Isotypic controls were used for each assay to determine non-
specific staining. Phenotypes were expressed as the percentages of
total cells analyzed by flow cytometry. Gating strategies for multipa-
rameter analyses were performed using side scatter vs. FL3 (peri-
dinin chlorophyll protein) (CD8⫹ cells) or side scatter vs. FL4 (allo-
phycocyanin) (CD4⫹ cells) using various combinations of
monoclonal antibodies. For quantification of adhesion molecule
density, the number of antibodies bound per cell was estimated
using flow cytometry with Quantibrite PE beads (Becton-Dickinson).
The Quantibrite PE beads were run using the same instrument
665

settings as used for the assay. The number of PE molecules per bead
was calibrated with the geometric mean of the bead peaks in linear
fluorescence, and the FL2 (PE) axis was converted into the number
of PE molecules bound per cell. The number of antibodies that bind
to the specific cell provides a good approximation of antigen
density.
To measure catecholamines, blood was collected on ice before
and immediately after the speech and exercise tasks and separated
in a refrigerated centrifuge. The plasma was stored at ⫺80°C until
assay. Epinephrine and norepinephrine were determined by ra-
dioenzymatic assay (30). The intra- and interassay coefficients of
variation for the assay are 6.5% and 11%, respectively. We gathered
complete catecholamine data on 43 of the 45 subjects.
Statistical Analysis
Data were analyzed using one-factor (time) repeated-measures
analysis of variance (SPSS statistical software, version 9.0). For
multiple comparisons, Bonferroni adjustment was performed.
RESULTS
The tasks induced significant SNS activation, indi-
cated by increased circulating catecholamine levels.
The speech task induced a significant increase in lev-
els of plasma norepinephrine (from 300 pg/ml (SD ⫾
123) at rest to 335 pg/ml (SD ⫾ 130) after the speech,
F(1,42) ⫽ 10.9, p ⫽ .002) and epinephrine (from 40
pg/ml (SD ⫾ 37) at rest to 70 pg/ml (SD ⫾ 144) after the
speech, F(1,42) ⫽ 3.5, p ⬍ .05). Exercise induced a
significant increase in levels of plasma norepinephrine
(from 404 pg/ml (SD ⫾ 172) at rest to 722 pg/ml (SD ⫾
342) after exercise, F(1,42) ⫽ 49, p ⬍ .001) and epi-
nephrine (from 52 pg/ml (SD ⫾ 32) at rest to 99 pg/ml
(SD ⫾ 94) after exercise, F(1,42) ⫽ 12, p ⫽ .001).
Leukocyte Subsets and Adhesion Molecule
Expression
The data for lymphocytes, monocytes, and granulo-
cytes are presented in Table 1. The speech task led to
increases in circulating levels of mixed (B, T, and NK
cells) lymphocytes (F(1,44) ⫽ 9.27, p ⬍ .001), mono-
cytes (F(1,44) ⫽ 5.93, p ⫽ .004), CD8⫹ T cells (F(1,44)
⫽ 10.07, p ⬍ .001), CD3⫺CD16⫹56⫹ NK cells (F(1,44)
TABLE 1. Leukocyte and Lymphocyte Subsets in Response to Public Speaking and Exercisea
Baseline Speech
Monocytes 433 (124) 472 (168)**
Granulocytes 3757 (1700) 3875 (1736)*
Lymphocytes 1826 (696) 2029 (715)***
Helper T cells (CD3⫹CD4⫹) 861 (357) 968 (440)*
Cytotoxic T cells (CD3⫹CD8⫹) 457 (224) 538 (274)***
NK cells (CD3⫺CD16⫹56⫹) 217 (269) 281 (289)***
a
Values are mean ⫾ SD (cells/␮l).
* p ⬍ .05, ** p ⬍ .01, *** p ⬍ .001 (all increases over baseline levels).
666
M. U. GOEBEL AND P. J. MILLS
⫽ 20.158, p ⬍ .001), granulocytes (F(1,44) ⫽ 4.237, p ⫽
.018), and CD4⫹ T cells (F(1,44) ⫽ 4.60, p ⫽ .013).
After the speech task, the number of CD8⫹CD62L⫺ T
cells (F(1,44) ⫽ 6.38, p ⫽ .003), CD4⫹CD62L⫺ T cells
(F(1,44) ⫽ 3.62, p ⫽ .031), and CD3⫺CD16⫹56⫹CD62L⫺
NK cells (F(1,44) ⫽ 8, p ⫽ .007) in the circulation were
increased (Table 2). CD4⫹CD62L⫹ T cells (F(1,44) ⫽ 4.29,
p ⫽ .017), CD8⫹CD62L⫹ T cells (F(1,44) ⫽ 4.82, p ⫽ .01),
and CD3⫺CD16⫹56⫹CD62L⫹ NK cells (F(1,44) ⫽ 11, p ⬍
.001) also increased above baseline levels. Moreover, the
numbers of lymphocytes (F(1,44) ⫽ 5.75, p ⫽ .004),
monocytes (F(1,44) ⫽ 5.42, p ⫽ .006), and granulocytes
(F(1,44) ⫽ 3.96, p ⫽ .023) expressing CD54 (CD54⫹) were
elevated.
Exercise lead to an increase in generally all leukocyte
and lymphocyte subsets, including monocytes (F(1,44) ⫽
45.34, p ⬍ .001), granulocytes (F(1,44) ⫽ 43.36, p ⬍ .001),
lymphocytes (F(1,44) ⫽ 98.71, p ⬍ .001), CD4⫹ T cells
(F(1,44) ⫽ 49.96, p ⬍ .001), CD8⫹ T cells (F(1,44) ⫽
46.12, p ⬍ .001), and CD3⫺CD16⫹56⫹ NK cells (F(1,44)
⫽ 91.71, p ⬍ .001) (Table 1).
Subsets not expressing CD62L, such as CD8⫹CD62L⫺
(F(1,44) ⫽ 37.7, p ⬍ .001), CD4⫹CD62L⫺ (F(1,44) ⫽ 23.3,
p ⬍ .001), and CD3⫺CD16⫹56⫹CD62L⫺ (F(1,44) ⫽ 12.3,
p ⬍ .001), were elevated on exercise (Table 2). Moreover,
circulating levels of cells expressing CD62L, such as
CD8⫹CD62L⫹ (F(1,44) ⫽ 32.12, p ⬍ .001), CD4⫹CD62L⫹
(F(1,44) ⫽ 49.79, p ⬍ .001), and CD3⫺CD16⫹56⫹CD62L⫹
(F(1,44) ⫽ 38, p ⬍ .001), were also elevated. In addition,
the numbers of lymphocytes (F(1,44) ⫽ 74.87, p ⬍ .001),
monocytes (F(1,44) ⫽ 26.34, p ⬍ .001), and granulocytes
(F(1,44) ⫽ 18.61, p ⬍ .001) expressing CD54 were
increased.
Leukocyte Subsets and Adhesion Molecule
Density
Adhesion molecule density varied among lympho-
cyte subsets (Table 3). The surface density of CD62L
only slightly and nonsignificantly decreased on lym-
phocyte subsets on the speech task (Table 3 and Fig. 1).
In contrast, on exercise, the density of CD62L was
Recovery Baseline Exercise Recovery
489 (134) 484 (138) 658 (189)*** 539 (198)
3702 (1653) 3981 (1632) 4835 (2132)*** 3947 (1868)
1904 (663) 2122 (731) 3000 (952)*** 2246 (749)
881 (351) 963 (386) 1205 (480)*** 997 (388)
484 (237) 537 (261) 800 (442)*** 589 (279)
232 (283) 291 (318) 614 (461)*** 334 (382)
Psychosomatic Medicine 62:664 – 670 (2000)
PSYCHOLOGICAL STRESS, EXERCISE, AND ADHESION

TABLE 2. Leukocyte and Lymphocyte Subsets According to Adhesion Molecule Expression in Response to Public Speaking and
Exercisea

Baseline Speech Recovery Baseline Exercise Recovery

CD8⫹CD62L⫹ 283 (139) 327 (176)** 299 (145) 322 (148) 430 (217)*** 340 (155)
CD8⫹CD62L⫺ 175 (132) 214 (131)** 188 (139) 219 (162) 379 (291)*** 243 (174)
CD4⫹CD62L⫹ 714 (322) 778 (352)* 731 (300) 792 (335) 972 (397)*** 792 (322)
CD4⫹CD62L⫺ 147 (95) 194 (168) 153 (101) 174 (116) 243 (181)*** 184 (128)
NKCD62L⫹ 150 (60) 201 (101)* 158 (81) 201 (63) 378 (120)*** 211 (80)
NKCD62L⫺ 47 (73) 79 (80)* 57 (78) 72 (68) 210 (144)*** 81 (78)
CD54⫹ lymphocytes 900 (357) 1011 (393)** 940 (421) 1050 (445) 1604 (681)*** 1173 (459)
CD54⫹ monocytes 424 (123) 463 (166)** 477 (131) 462 (153) 632 (209)*** 527 (195)
CD54⫹ granulocytes 2397 (1271) 2532 (1344)* 2358 (1166) 2625 (1290) 3123 (1844)*** 2553 (1368)

a
Values are mean ⫾ SD (cells/␮l).
* p ⬍ .05, ** p ⬍ .01, *** p ⬍ .001 (all increases over baseline levels).

significantly lower than the baseline level before exer-
cise on mixed lymphocytes (F(1,44) ⫽ 20.14, p ⬍ .001),
CD8⫹ cells (F(1,44) ⫽ 24.62, p ⬍ .001), and CD4⫹ cells
(F(1,44) ⫽ 7.85, p ⫽ .001) and returned near baseline
levels during the recovery phase (Table 3 and Fig. 1).
In contrast, the density of CD11a on mixed lympho-
cytes was markedly increased after both the speech
(F(1,44) ⫽ 6.67, p ⫽ .002) and exercise (F(1,44) ⫽
40.54, p ⬍ .001) tasks (Fig. 2). Similar to CD62L den-
sity, CD11a density returned to near the baseline level
15 minutes after both tasks.
Half of the mixed lymphocytes and about 95% of
monocytes expressed CD54 before the speech and ex-
ercise tasks. Interestingly, the surface density of CD54
remained unchanged throughout the two experiments.
DISCUSSION
This study examined the effects of psychological
stress and exercise on leukocytes and lymphocyte sub-
sets and their differential changes according to adhe-
sion molecule expression. We replicated the existing
findings of leukocytosis after such stressors as a speak-
ing task and exercise (1), because exercise and psycho-
logical stress resulted in a marked elevation in all
leukocyte and lymphocyte subsets. The exercise task,
however, had more prominent effects than the speak-
ing task, which is consistent with the larger catechol-
amine increase in response to exercise (31).
After exercise, the surface density of CD62L was
decreased on mixed lymphocytes and CD4⫹ and CD8⫹
T cells; CD62L density returned to near baseline levels
15 minutes later. Because we did not assess levels of
soluble CD62L in the circulation, we cannot exclude
the possibility of shedding, which is a limitation of our
study. There is mixed evidence on the effects of SNS
activation on levels of soluble adhesion molecules.
There is some evidence of CD62L shedding due to
exercise (14), but some studies show an exercise-in-
duced increase of soluble ICAM-1 levels (15, 32).
Other studies show no change in levels of soluble
ICAM-1, soluble CD62L, or soluble CD62E (E-selectin)
after infusion of adrenergic agonists (5, 33). In this
study, ICAM-1 density did not significantly change on
lymphocytes, monocytes, or granulocytes. However,
the absolute numbers of CD54⫹ lymphocytes and

TABLE 3. Leukocyte and Lymphocyte Adhesion Molecule Density in Response to Public Speaking and Exercisea

Baseline Speech Recovery Baseline Exercise Recovery

CD62L on lymphocytes 13018 (3872) 12329 (3649) 12316 (3560) 12062 (3639) 10624 (3516)***b 11805 (3169)
CD62L on CD4⫹ 13154 (3961) 12671 (3866) 12459 (3632) 12021 (3789) 11291 (3918)***b 12105 (3403)
CD62L on CD8⫹ 11521 (3974) 10739 (3874) 10826 (3585) 10394 (3572) 8762 (3510)***b 9993 (3216)
CD54 on lymphocytes 1086 (307) 1060 (277) 1045 (266) 1039 (279) 1051 (267) 1208 (876)
CD54 on monocytes 4621 (990) 4552 (983) 4678 (961) 4648 (1030) 4712 (1034) 4686 (1265)
CD54 on granulocytes 657 (193) 657 (178) 659 (194) 685 (191) 694 (248) 1468 (4599)
CD11a on lymphocytes 22737 (6395) 23843 (6686)**c 22850 (6276) 23713 (6968) 27481 (8003)***c 24910 (7741)
CD11a on monocytes 37667 (6747) 37268 (7151) 36696 (8845) 36198 (6627) 35899 (6330) 35710 (8282)
CD11a on granulocytes 8848 (1708) 8749 (1679) 8762 (1739) 9076 (1968) 9115 (1866) 9060 (2037)

a
Values are mean ⫾ SD (number of PE molecules bound per cell).
b
Decrease below baseline level with exercise.
c
Increase over baseline level.
** p ⬍ .01, *** p ⬍ .001.

Psychosomatic Medicine 62:664 – 670 (2000) 667


Fig. 1. L-selectin (CD62L) density (number of PE molecules bound
per cell) in response to a speaking and an exercise task. In
response to public speaking (top), the surface density of
CD62L was decreased, but not significantly, on mixed lym-
phocytes, CD8⫹ cytotoxic cells, and CD4⫹ helper T cells. In
response to exercise (bottom), the surface density of CD62L
was significantly decreased on mixed lymphocytes, CD8⫹
cytotoxic cells, and CD4⫹ helper T cells (p values ⬍ .001).
monocytes, but not granulocytes, increased. In con-
trast to previous findings (10, 13), both CD62L⫺ and
CD62L⫹ T lymphocytes increased after the speaking
task and exercise, although the relative increase was
more marked for CD62L⫺ cells. Kurokawa et al. (10),
however, used a 60-minute bicycle exercise task with
blood first drawn 30 minutes into exercise, which may
explain the variations in the findings.
Lymphocyte CD11a density was higher after the
speech and exercise tasks. The fact that lymphocyte
CD62L density was decreased and lymphocyte CD11a
density was simultaneously increased is likely due, at
668
M. U. GOEBEL AND P. J. MILLS
Fig. 2. LFA-1 (CD11a) density (number of PE molecules bound per
cell) on lymphocytes in response to speaking and exercise
tasks. The surface density of CD11a on lymphocytes was
greater after both the exercise (p ⬍ .001) and speaking (p ⬍
.01) tasks.
least in part, to redistribution of the lymphocyte sub-
sets. We have previously shown that infusion of iso-
proterenol (a ␤-agonist) preferentially mobilizes T
cells of the memory/activated phenotype, whereas
propranolol (a ␤-blocker) diminishes these effects (33).
In general, naive lymphocytes (CD45RA⫹CD45RO⫺)
are mostly CD62Lhigh⫹ cells and lose the CD62L ex-
pression on encounter with antigen, whereas memory
T cells (CD45RA⫺CD45RO⫹) show low CD62L expres-
sion and increased density of CD11a (16). On activa-
tion of T cells, CD62L is downregulated with a de-
crease of 90% within the first 4 hours of activation in
vitro (34). Therefore, activated and naive T cells can be
distinguished by their surface adhesion molecule ex-
pression. However, memory and effector T cells share
the same pattern of surface markers, including CD62L
(35, 36). We hypothesize that differences in homing
and migration of the activated/memory phenotype
contribute to the stress-induced change in CD62L and
CD11a expression. Memory T cells might be retained
to a larger amount in the spleen than in the lymph
nodes (16) and provide the ability for a fast mobiliza-
tion of already activated lymphocytes in conditions
such as acute activation of the SNS.
The data extend earlier findings on exercise and
adhesion molecule expression (37, 38), showing that
the phenotypic characteristics of circulating cells after
exercise are similar to those that invade on exposure to
an acute psychological stressor. In general, the psycho-
logical stressor led to a somewhat similar profile of
expression of adhesion molecules as compared with
exercise. Both stimuli led to greater expression of
CD11a on circulating lymphocytes. These parallel
findings in the profile of CD11a and in part of CD62L
expression resulting from exercise and psychological
Psychosomatic Medicine 62:664 – 670 (2000)
PSYCHOLOGICAL STRESS, EXERCISE, AND ADHESION
stress may be related to activation of the immune sys-
tem in the sense of a fight-flight response. Besides cells
of the nonspecific immune response (eg, NK cells)
entering into circulation, T lymphocytes that have al-
ready seen antigen emerge.
Recent studies suggest that the chronic psychologi-
cal stress of caregiving and burnout at the workplace
affect adhesion molecule expression and leukocyte ad-
hesiveness (22, 39). Caregiving and burnout are also
associated with immunologic decrements and in-
creased cardiovascular disease (22, 39 – 41). Given the
important effect of adhesion molecules on circulating
cells in the inflammation response, including athero-
sclerotic processes (25–27), one can speculate that
stress-mediated effects on adhesion molecules may
have clinical relevance.
The authors are grateful to Michael G. Ziegler, MD,
for analyzing the catecholamines and to Jose Loredo,
MD, for obtaining the histories and performing the
physical examinations. In addition, we are grateful to
the Immunogenetics Laboratory at the Veterans Affairs
Medical Center for leukocyte determinations. This
work was supported by Grants MO1-RR00827,
HL-57265, and AG-13332 from the National Institutes
of Health.
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