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Clinical Research Center for Periodontal Diseases, Virginia Commonwealth University School of Dentistry, Richmond, VA 23298
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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) and monocyte-derived dendritic cells
(MDDC) come from a common precursor, they are distinct cell types. This
report compares the two cell types with respect to the metabolism of
platelet-activating factor (PAF), a biologically active lipid mediator.
These experiments were prompted by our studies of localized juvenile
periodontitis, a disease associated with high IgG2 production and a
propensity of monocytes to differentiate into MDDC. As the IgG2 Ab
response is dependent on PAF, and MDDC selectively induce IgG2
production, we predicted that PAF levels would be higher in MDDC than
in M. To test this hypothesis, human MDDC were prepared by treating
adherent monocytes with IL-4 and GM-CSF, and M were produced by
culture in M-CSF. Both M and MDDC synthesized PAF; however, MDDC
accumulated significantly more of this lipid. We considered the
possibility that PAF accumulation in MDDC might result from reduced
turnover due to lower levels of PAF acetylhydrolase (PAFAH), the enzyme
that catabolizes PAF. Although PAFAH increased when monocytes
differentiated into either cell type, MDDC contained significantly less
PAFAH than did M and secreted almost no PAFAH activity. The reduced
levels of PAFAH in MDDC could be attributed to lower levels of
expression of the enzyme in MDDC and allowed these cells to produce
PGE2 in response to exogenous PAF. In contrast, M did
not respond in this manner. Together, these data indicate that PAF
metabolism may impinge on regulation of the immune response by
regulating the accessory activity of MDDC. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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)3 and
monocyte-derived dendritic cells (MDDC). Both monocytes and M are
components of the mononuclear phagocyte system. M are important
phagocytic cells that capture invading microbes and participate in
eliminating them by either direct cytolysis or by presenting peptides
to T cells and inducing specific immunity. M also secrete cytokines
and lipid mediators that regulate the immune response, including
TNF-
, IL-1, IL-6, platelet-activating factor (PAF), and
PGE2 (1, 2, 3, 4). Like M, immature
MDDC are highly phagocytic cells, and Ag capture triggers MDDC
maturation. Mature MDDC migrate to secondary lymphoid tissues, where
they exhibit increased expression of the class II MHC proteins and
costimulatory molecules associated with Ag presentation. Thus, like
M, mature MDDC are highly efficient APC. MDDC also regulate the
immune response, but they differ from M in that they can either
enhance or suppress cell-mediated immunity in response to environmental
cues (5, 6). Recent studies indicate that MDDC can
regulate the immune response by secreting cytokines (such as IL-12),
chemokines, and PGE2 (5, 7).
This report compares the changes in platelet-activating factor (PAF)
metabolism that occur when monocytes differentiate into either M or
MDDC. Our interest in PAF metabolism in MDDC comes from studies of the
immune response in localized juvenile periodontitis (LJP), a
periodontal disease characterized by its circumpubertal onset and
characteristic localized loss of supporting tissues around first molars
and incisors (8). In a previous study we demonstrated that
monocytes from LJP subjects have an increased propensity to
differentiate into MDDC, while monocytes from healthy non-periodontitis
(NP) subjects primarily differentiate into M (9).
Moreover, LJP subjects have elevated levels of IgG2 Ab in their sera,
and LJP monocytes secrete cytokines that selectively promote the
production of this subclass of Ab (10, 11). Most notably,
the monocyte-derived lipid mediators, PAF and
PGE2, were shown to induce IgG2 production, but
had no effect on the production of IgG1 in a pokeweed mitogen-driven in
vitro culture system. Furthermore, highly enriched MDDC cultures were
shown to have a similar selective effect on IgG2 production
(9). Together, these studies suggest that the outgrowth of
MDDC in cultures of LJP monocytes may have important implications for
the regulation of Ig subclass responses and that this regulation may be
mediated through the levels of lipid mediators in the cultures.
Although it is well established that LJP monocytes secrete more
PGE2 than NP monocytes (12), PAF
metabolism has not yet been compared in these two populations. A
previous study demonstrated that PAF levels change dramatically when
monocytes differentiate into M (3). Although both M
and monocytes can synthesize PAF, monocytes accumulate considerably
more of this lipid mediator. This difference can be attributed to the
expression of PAF acetylhydrolase (PAFAH), a catabolic phospholipase
A2 that selectively hydrolyzes PAF. The activity
of this enzyme increases nearly 300-fold when monocytes differentiate
into M (3). Given the apparent connections between
MDDC, PAF, and the production of IgG2 in our model system, we
hypothesized that the expression of this enzyme might be considerably
lower in MDDC than in mature M. To investigate this possibility, we
compared PAF metabolism in highly enriched cultures of MDDC and M.
Our data indicate that MDDC do indeed accumulate more PAF than do M
and that this accumulation is associated with a reduction in the
expression of PAF acetylhydrolase (PAFAH). Moreover, while MDDC
synthesize PGE2 in response to nanomolar
concentrations of PAF, M make no comparable response, presumably
because the exogenous PAF is readily catabolized by M-derived PAFAH.
Together, these data indicate that the differentiation pathway of
monocytes has important implications for the levels of PAF and other
lipid mediators that are available to regulate the immune response.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Human studies were performed in compliance with all relevant federal guidelines and the institutional policies of Virginia Commonwealth University. Buffy coat preparations were obtained from Virginia Blood Services (Richmond, VA) and were used within 24 h of blood draw. In some experiments subjects for study were located through the Clinical Research Center for Periodontal Disease, School of Dentistry, Virginia Commonwealth University (Richmond, VA). Patients with LJP were 35 years old or less and had localized patterns of severe periodontal destruction limited to the first molar or incisor teeth and up to two additional teeth. The NP control subjects were age- and race-matched and had no evidence of attachment loss, except for recession on the buccal surface of anterior teeth at no more than one site and no pockets >3 mm. All NP and LJP subjects were nonsmokers.
Isolation of leukocytes from peripheral blood (PBL)
Thirty milliliters of heparinzed or citrated human peripheral blood was layered over 15 ml of Lymphocyte Separation Media (ICN Pharmaceuticals, Aurora, IL) and centrifuged at 400 x g for 30 min. PBL were then collected from the interface and washed with RPMI medium. To obtain adherent monocytes, the PBL were cultured on plastic plates for 1 h at 37°C in 1 ml of RPMI containing 10% heat-inactivated FCS. Extensive washing was performed to remove nonadherent cells. In all cases cell viability was at least 90%.
Macrophage cell cultures
Adherent monocytes were cultured for 7 days in RPMI containing
10% heat-inactivated human AB serum (BioWhittaker, Walkersville, MD),
50 µg/ml of gentamicin (Invitrogen/Life Technologies, Gaithersburg,
MD), and 2 mM glutamine (Invitrogen/Life Technologies). In most cases
the cell cultures were treated with 1000 U/ml of recombinant human
M-CSF (R&D Systems, Minneapolis, MN) to induce differentiation to the
M phenotype. Cell cultures were maintained at 37°C in 7.5%
CO2 and 100% humidity. The phenotypes of the
cell cultures were confirmed through FACS analyses of
CD14high, class II
MHCmoderate, and
CD86moderate expression (data not shown).
MDDC cultures
Adherent monocytes were cultured for 7 days in RPMI containing 10% heat-inactivated FCS, 50 µg/ml of gentamicin (Invitrogen/Life Technologies), and 2 mM glutamine (Invitrogen/Life Technologies) in the presence 500 U/ml of recombinant human IL-4 and 800 U/ml of recombinant human GM-CSF (R&D Systems). To induce maturation of MDDC, 100 ng/ml of Escherichia coli LPS was added on day 5, and MDDC were allowed to mature for 2 additional days (13). Cell cultures were maintained at 37°C in 7.5% CO2 and 100% humidity. The phenotypes of the cell cultures were confirmed through FACS analyses of CD14low, class II MHC high, and CD86 expression high (data not shown).
Preparation of conditioned medium
M and MDDC were incubated overnight in serum-free RPMI medium
at 37°C in 7.5% CO2 and 100% humidity. The
cell-free medium was harvested and centrifuged to remove floating
cells, and supernatant fluids were collected and stored at -80°C
until used.
PAF accumulation assay
To measure PAF accumulation, a metabolic labeling assay was
performed as previously described (14). Adherent M and
MDDC were cultured in 1 ml of HBSS (Cellgro, PeproTech, Rocky Hill, NJ)
containing 25 µCi of [3H]acetic acid (NEN,
Boston, MA; 2.5 Ci/mmol) for 50 min at 37°C. The cells were harvested
and washed twice with HBSS to remove excess radiolabel. Cellular lipids
were extracted and [3H]PAF was separated
on TLC plates using a previously described method (14).
PAF was identified based on comigration with authentic PAF. The PAF
band was scraped from the TLC plate, and radiolabeled PAF was
quantified by scintillation counting and normalized to cell protein.
This assay measures total PAF accumulation and does not distinguish
between alkyl-PAF and acyl-PAF.
PAFAH assay
PAFAH activity was measured using a previously described method (15) with minor modifications. The substrate consisted of 50 µM 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF; obtained from Avanti Polar Lipids, Alabaster, AL) with 0.05 µCi of hexadecyl-2-acetyl-sn-glyceryl-3-phosphocholine, 1-O-[acetyl-(N)-3H] (NEN/PerkinElmer; 13.5 Ci/mmol) added as a tracer. Substrate was incubated together with enzyme source (cell homogenate or conditioned medium) in a total volume of 500 µl. The reactions were incubated at 37°C for 30 min and were terminated by the addition of 500 µl of 14% TCA. Samples were incubated at 4°C for 10 min and then centrifuged at 1000 x g for 15–20 min at 4°C. Four hundred microliters of the supernatant containing released [3H]acetate was mixed with 5 ml of BioSafe II scintillation cocktail (RPI, Mount Prospect, IL), and radiolabeled acetate was quantified by scintillation counting. The reactions were performed in triplicate, and a reaction without enzyme was used as a control for nonenzymatic hydrolysis. All assays were performed under conditions in which substrate hydrolysis was linear with respect to both enzyme input and time.
Real-time PCR
Real-time PCR was performed by the Nucleic Acid Research
Facility at Virginia Commonwealth University. RNA was prepared from
M or MDDC with the TRIzol RNA isolation reagent (Invitrogen/Life
Technologies). The primers for the real-time PCR were
5'-CCCAGGGACCCCAGTTC-3' and 5'-CATGTGCTTTTCTGCCTCTGC-3',
complementary to bp 84–100 and 179–200, respectively. The probe was
5'-CTCCGCGCCG CGCCTGAGAGACTAAGC-3' (complementary to bp 110–137).
The probes and primers were designed using the Primer Express 1.5
version (Applied Biosystems, Foster City, CA). The TaqMan probe
(Applied Biosystems) was labeled in the 5' end with FAM (fluorescein)
and in the 3' end with TAMRA.
The experiments were performed with the ABI PRISM 7700 Sequence
Detection System (PE Applied Biosystems, Foster City, CA) using the
TaqMan One Step PCR Master Mix Reagents Kit (P/N:4309169). All samples
were tested in triplicate under the conditions recommended by the
fabricant. The cycle threshold was determined to provide the
optimal standard curve values (0.98–1.0). The signal for PAFAH mRNA
expression was normalized to 
-actin expression (TaqMan Reagent
Endogenous Control).
Western blot
Proteins in M, MDDC, and mature MDDC cell homogenates were
separated by SDS-PAGE, and the proteins were transferred onto
nitrocellulose using standard methods (16). PAFAH protein
was detected with an Ab directed against the C terminus of plasma PAFAH
(Cayman Chemical, Ann Arbor, MI). An Ab against Raf-1 (Santa Cruz
Biotechnologies, Santa Cruz, CA) was used as a protein loading control.
Protein A-HRP and the ECL Western blotting detection system (both from
Amersham Pharmacia Biotech, Arlington Heights, IL) were used. In a
peptide blocking experiment anti-PAFAH Ab was incubated with 10
µg/ml of PAFAH blocking peptide (Cayman Chemical) for 1 h at
room temperature before addition to the blot. This treatment eliminated
the 45-kDa PAFAH band (data not shown). In addition to the 45-kDa PAFAH
band, anti-PAFAH recognized a protein of 
50 kDa, which was
eliminated by the peptide. This band may be the glycosylated form of
PAFAH that has recently been described (17).
PGE2 assay
To measure PGE2 production, M and MDDC
were cultured overnight in RPMI containing 5 µg/ml of fraction V BSA
(Sigma-Aldrich, St. Louis, MO) and various doses of PAF (Avanti Polar
Lipids) or methylcarbamyl PAF (cPAF; obtained from Biomol, Plymouth
Meeting, PA). The conditioned media were collected and released.
PGE2 was quantified with a
PGE2 Enzyme Immunoassay Kit (Assay Designs,
Ann Arbor, MI). PGE2 production was
normalized to the cellular protein recovered from the cultures. Protein
mass was determined with the protein assay reagent from Bio-Rad
(Hercules, CA).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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We hypothesized that larger quantities of PAF might be available
in MDDC cultures than in M. To test this question, M and MDDC
were metabolically labeled with [3H]acetate,
cell-associated lipids were extracted, and accumulated alkyl- and/or
acyl-PAF was quantified by scintillation counting (as described in
Materials and Methods). Both M and MDDC
synthesized PAF (Fig. 1
). However, MDDC
accumulated 3 times more PAF than did M
(p = 0.039).
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than MDDC
The accumulation of PAF in MDDC could be the result of increased
synthesis of the lipid mediator or might be related to a reduction in
its catabolism by PAFAH, a phospholipase A2 that
selectively hydrolyzes PAF. To address the question of PAFAH, we
quantified the PAFAH activity secreted by M and MDDC. As is shown in
Fig. 2, M secreted significantly more
PAFAH than did immature MDDC (17-fold difference; p <
0.0001). A previous study demonstrated that PAFAH expression increases
dramatically when monocytes differentiate into M (3).
However, the expression of PAFAH during MDDC differentiation has not
been described. Based on the results shown in Fig. 2, we predicted that
the increase in PAFAH expression would be less pronounced in
differentiating MDDC than in M. To address this, PAFAH activity was
measured in homogenates of monocytes, M, MDDC, and mature MDDC. A
representative experiment is shown in Fig. 3. PAFAH activity increases when
monocytes differentiate into either M or MDDC. However, PAFAH
activity is 4-fold higher in homogenates of M than in MDDC
(p < 0.00001). Both cell-associated and
secreted PAFAH activities were similar in MDDC and mature MDDC. In
addition to PAFAH, M express other forms of
PLA2 that preferentially hydrolyze phospholipids
with longer sn-2 acyl chains. (18). Thus, we
cannot rule out the possibility that other PLA2s
contribute to the hydrolysis of PAF in MDDC and M cell homogenates.
In fact, this may explain why the ratio of catabolic activity in M
vs MDDC is lower in the cell homogenates (Fig. 3) than when secreted
activity is measured (Fig. 2). Nevertheless, these experiments strongly
suggest that enhanced accumulation of PAF in MDDC can be explained by a
reduction in PAF catabolism and that this can be at least partially
attributed to a reduction in its catabolism by PAFAH.
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than MDDC
To determine whether differences in PAFAH activity between M
and MDDC could be attributed to differences in expression, we
quantified PAFAH protein and mRNA in M and MDDC. PAFAH mRNA
expression was quantified by real-time PCR and was normalized to the
expression of -actin. As is shown in Fig. 4, PAFAH mRNA was at least 5 times higher
in M than MDDC or mature MDDC (p = 0.003 and
0.0004, respectively). PAFAH protein expression was quantified by
Western blot analysis with a polyclonal Ab directed against the C
terminus of plasma PAFAH. As shown in the inset to Fig. 4, PAFAH
protein expression was higher in M than MDDC or mature MDDC. Thus,
the expression of PAFAH protein and mRNA in MDDC and M was
consistent with differences in PAFAH activity in these cell types.
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As MDDC contained less PAFAH activity than M, we predicted that
PAF turnover would be low in these cells and that they would respond
more readily to low concentrations of exogenous PAF than would M. To
test this hypothesis, M and MDDC were treated with various
concentrations of PAF, and PGE2 production was
measured as explained in Materials and Methods. As
illustrated in Fig. 5A,
exogenous PAF induced a concentration-dependent increase in
PGE2 production in MDDC. In contrast, the
addition of exogenous PAF to M had no comparable effect. We
hypothesized that this failure to respond could be attributed to the
presence of high levels of PAFAH in M cell cultures, as the enzyme
catabolizes PAF and thereby limits the ability of the cells to respond
to this lipid mediator. To test this possibility, M and MDDC were
treated with cPAF (a PAFAH-resistant PAF analog), and
PGE2 production was measured. As shown in Fig. 5B, both M and MDDC produced PGE2
in response to cPAF stimulation in a dose-dependent manner. In fact,
the response of M to low concentrations of cPAF was more robust than
that of MDDC, although both cell types produced similar amounts of
PGE2 in response to 100 nM cPAF. The effect of
exogenous PAF on mature MDDC was also determined. Although mature
resting MDDC produced larger quantities of PGE2
than did immature MDDC (data not shown), exogenous PAF did not
stimulate increased PGE2 production (fold
induction, 1.0 ± 0.2 (mean ± SE)). This is most likely due
to the loss of the PAF receptor during MDDC maturation
(19), which renders mature MDDC unresponsive to PAF
treatment.
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As noted above, our studies were prompted by the observation that
LJP monocytes exhibit a propensity to differentiate into MDDC when
cultured for 4 days in human serum (9). The presence of
MDDC in LJP monocyte cultures is believed to augment IgG2 production,
possibly by promoting increased PAF accumulation. As MDDC contained
less PAFAH than did M, we reasoned that PAFAH levels would be lower
in cultures of LJP monocytes than in cultures of NP monocytes. To test
this hypothesis, LJP and NP monocytes were cultured for 4 days in human
serum, and PAFAH activity was measured in cell homogenates. As shown in
Fig. 6, homogenates of LJP monocyte
cultures do indeed contain less PAFAH activity than NP monocytes (37%
decline; p < 0.05). This observation is consistent
with our hypothesis that the differentiation of LJP monocytes to MDDC
may induce IgG2 production by regulating PAF levels.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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and MDDC, two immune cell types that differentiate
from a common monocyte precursor. As is illustrated in Fig. 1
, MDDC
accumulate 3-fold more PAF than M. The availability of PAF is
determined both by the rate of its synthesis and its degradation by
PAFAH, a calcium-independent phospholipase A2
that selectively hydrolyzes the sn-2 acyl chain of PAF to
generate biologically inactive lyso-PAF (18). As shown in
Fig. 3, PAFAH activity increases when monocytes differentiate into
either M or MDDC. However, M contain 4 times more PAFAH
activity than MDDC, and this may allow MDDC to accumulate more PAF.
More remarkably, M secrete 17-fold more PAFAH activity than do
MDDC (Fig. 2), and this may explain why MDDC respond to exogenous PAF
while M fail to do so (Fig. 5). As shown in Fig. 4, both PAFAH mRNA
and protein expression are lower in MDDC than in M. These data are
consistent with the difference in PAFAH activity in the two cell types
and indicate that the reduction in PAFAH activity in MDDC is a result
of lower expression of the enzyme.
The expression of PAFAH is known to be susceptible to modulation by
both host-derived cytokines and pro-inflammatory products derived from
bacteria (20). For example, both IFN-
(a host-derived,
pro-inflammatory cytokine) and LPS (a component of Gram-negative
bacteria) have been shown to suppress the transcriptional activity of
the PAFAH promoter. Interestingly, mouse DC have been shown to produce
IFN- in response to IL-12 (21), suggesting that these
cells may actively antagonize the synthesis of PAFAH. In contrast,
transcriptional activity is induced by PAF itself, suggesting the
existence of a feedback mechanism that maintains the levels of this
biologically active lipid (20). Other
monocyte/M-derived cytokines, including IL-1, TNF-, and IL-6
and the anti-inflammatory cytokine IL-4 have no effect on
transcription of the PAFAH gene (20). It is possible that
the expression of PAFAH is modulated by the cytokines that are used to
induce monocyte differentiation to M (M-CSF) and MDDC (GM-CSF). To
this end, these cytokines are reported to have modest effects on PAFAH
secretion by mature monocyte-derived M (20). However,
their effects on PAFAH expression during monocyte differentiation are
not yet known. Based on our observations, we predict that during
differentiation, the expression of PAFAH may be induced by both M-CSF
and IL-4/GM-CSF, but that M-CSF is the more potent inducer of
expression. Verification of this hypothesis awaits further studies in
our laboratory.
Although it is well established that primed macrophages both produce
and respond to PAF and other pro-inflammatory lipids (4, 3, 22), only a few previous studies have investigated the ability
of MDDC to produce and respond to lipid mediators. Like macrophages,
immature MDDC respond to PAF with increases in intracellular calcium
and polymerization of the actin cytoskeleton (19).
Interestingly, these responses do not occur in mature MDDC due to the
loss of PAF receptor expression upon maturation (19). This
is consistent with our observation that PAF elicits
PGE2 production by immature MDDC, but not by
mature MDDC (data not shown). Our data are also in line with a growing
body of evidence suggesting that MDDC are a potential source of
eicosanoids. Unlike M that only express the inducible form of
cyclooxygenase (COX2) after activation, resting MDDC have been shown to
constitutively express both COX1 and COX2 and to produce prostanoids,
PGE2 in particular, although in lower amounts
than macrophages (7). This PG, in turn, has dramatic
effects on the biology of MDDC. PGE2 and other
COX-derived products may induce the maturation of MDDC and thereby
augment their ability to stimulate all T cells (7). Most
studies suggest that PGE2 treatment of MDDC
shifts these cells from inducing a pro-inflammatory Th1 response to a
Th2 response (23, 24, 25). However, another study has
demonstrated that nanomolar concentrations of
PGE2 can induce IFN- production by
Ag-stimulated murine Th1 cells (26), and we have recently
confirmed this in a human
system.4 Thus, it is
possible that the PAF-stimulated MDDC could induce a Th1 response
through the low levels of PGE2 that are produced
by these cells. Clearly, additional experiments are necessary to
delineate the roles of PAF and PGE2 in MDDC
biology and to determine the relevance of these to the immune
response.
Although M and MDDC originate from a common monocyte precursor, they
have distinct, but overlapping, functions. Our studies indicate that
PAF metabolism is another aspect that is somewhat different in MDDC and
M biology. This difference may have important implications for both
the inflammatory response and the production of IgG2 Abs. Our studies
of PAF metabolism in M and MDDC were prompted by our investigations
of the immune response in patients with LJP, a disorder that is
associated with a number of abnormalities in the myeloid compartment
(10, 12, 27, 28, 29), including a propensity of monocytes to
differentiate into MDDC (9). LJP subjects also exhibit
high levels of circulating IgG2, and this subclass of Ab is thought to
lessen the severity of their disease (30, 31). We have
also shown that the IgG2 Ab response is selectively induced by PAF and
enriched cultures of MDDC (9, 10). The present study
extends our knowledge of the regulation of the IgG2 Ab response in
periodontal disease and provides us with another clue regarding the
relationship of monocytes to this response. Although PAFAH expression
increases when monocytes differentiate into either M or MDDC,
expression is at least 3-fold lower in MDDC (Fig. 4), and these cells
secrete very little of the catabolic enzyme (Fig. 3). Hence, in
periodontally healthy (NP) subjects in whom monocytes differentiate
primarily into macrophages, large amounts of PAFAH are secreted,
thereby limiting the availability of PAF and the production of IgG2. In
contrast, the propensity of LJP monocytes to differentiate into MDDC
results in lower levels of PAFAH (Fig. 6), and this allows PAF to
accumulate and promote the production of a protective IgG2 Ab response.
We are currently performing experiments to further delineate the role
of PAF in the IgG2 Ab response and to identify the mechanisms that skew
monocyte differentiation toward the MDDC phenotype in LJP subjects.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Suzanne E. Barbour, Department of Microbiology and Immunology, Box 980678, Richmond, VA 23298-0678. E-mail address: sbarbour{at}hsc.vcu.edu
3 Abbreviations used in this paper: M, macrophage; COX, cyclooxygenase; LJP, localized juvenile periodontitis; MDDC, monocyte-derived dendritic cell; NP, non-periodontitis; PAF, platelet-activating factor; PAFAH, platelet-activating factor acetylhydrolase; cPAF, methylcarbamyl PAF.
4 S. Tanaka, E. Suzanne, A. M. Best, H. A. Schenkein, and J. G. Tew. Prostaglandin E2-mediated regulation of IgG2 via interferon-. Submitted for publication.
Received for publication April 4, 2002. Accepted for publication October 23, 2002.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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, IL-6, and TNF by adherent mononuclear cells from early onset periodontitis patients. J. Periodontol. 65:139.[Medline]
production by dendritic cells. J. Immunol. 164:64. production by antigen-stimulated type 1 helper T cells. Cell. Immunol. 194:21.[Medline]
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