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. Author manuscript; available in PMC: 2012 Apr 24.
Published in final edited form as: Am J Rhinol Allergy. 2010 Jan-Feb;24(1):11–16. doi: 10.2500/ajra.2010.24.3386

Evaluation of the presence of B-cell attractant chemokines in chronic rhinosinusitis

Monica Patadia 1, Julian Dixon 1, David Conley 1, Rakesh Chandra 1, Anju Peters 2, Lydia A Suh 2, Atsushi Kato 1,2, Roderick Carter 2, Kathleen Harris 2, Leslie Grammer 2, Robert Kern 1, Robert Schleimer 2
PMCID: PMC3335771  NIHMSID: NIHMS289573  PMID: 20109310

Abstract

Background

B-cell responses may play a role in the pathogenesis of nasal polyposis via local IgA and IgE production and activation of eosinophils and mast cells. B-cell attracting chemokines may therefore have relevance in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs)

Methods

Polyp and inferior turbinate tissues were obtained from CRSwNPs, CRS without NPs (CRSsNPs), and control patients; ELISA and reverse-transcription polymerase chain reaction were used to detect levels of protein and mRNA for selected B-cell chemokines (B-cell attracting chemokine 1 [CXCL13/BCA-1/BLC]), thymus expressed chemokine (CCL25/TECK), mucosae-associated epithelial chemokine (CCL28/MEC), stromal cell–derived factor-1alpha (CXCL12/SDF-1alpha), and selected chemokine receptor genes (CXCR4, CXCR5, and CXCR7).

Results

BCA-1 and SDF-1alpha protein levels were significantly increased in polyp tissue compared with turbinate tissue from CRSsNP patients and controls (p < 0.05 and p < 0.01, respectively). Differences in TECK and MEC were not significant. For mRNA, expression of BCA-1 was significantly up-regulated in polyp tissue and levels correlated with CD20 mRNA expression. Additionally, significant up-regulation of mRNA for the SDF-1alpha receptors CXCR7 and CXCR4 was detected in polyps, while there was a trend for up-regulation of the BCA-1 receptor CXCR5.

Conclusion

Elevated levels of the BCA-1 and SDF-1alpha and their receptors may account for an increased presence of B cells and their products, contributing to eosinophilic inflammation in patients with CRSwNP.

Keywords: B-cell recruitment, CCL25/TECK, CCL28/MEC, chemokines, chronic rhinosinusitis, CXCL12/SDF-1alpha, CXCL13/BCA-1, nasal polyposis

Chronic rhinosinusitis (CRS) is a common clinical syndrome characterized by persistent, symptomatic mucosal inflammation. Subjective and objective criteria have been established to define CRS, but the etiology and pathogenesis remain incompletely understood.1,2 CRS is commonly subdivided into two types, CRS with nasal polyps (CRSwNPs) and CRS without NPs (CRSsNPs), as determined by endoscopic and radiographic evaluations. In western countries, CRSwNP is typically characterized by a skewed TH2 pattern of inflammation and a marked tissue eosinophilia.3,4 Eotaxins and IL-5 have been implicated in the induction of this mucosal eosinophilia in CRSwNP patients because these factors are significantly elevated in polyp tissue compared with CRSsNP tissue or sinonasal tissue from healthy subjects.5,6 Although these reports account for the accumulation and persistence of eosinophils in polyp tissue, they do not address the triggers for eosinophil degranulation or the accumulation of other inflammatory cell types, which are presumably also significant factors in the pathophysiology of CRSwNPs.

Recent reports suggest that B-cell accumulation, local B-cell class switch recombination, and local immunoglobulin production may be of great importance to mucosal inflammatory diseases in the lower and upper airway as well. B-cell and plasma cell numbers as well as IgE and IgA concentrations have been reported to be increased in polypoid sinonasal mucosal tissue from patients with CRSwNPs when compared with controls or CRSsNPs.4,7–9 Furthermore, it is well established that mucosal B cells undergo class switch recombination to express IgA, and that IgA can serve as a trigger for eosinophil degranulation by binding to surface receptors present on these cells. These findings suggest a possible link between local B cells, IgA, and eosinophilic degranulation in CRSwNPs.9 The mechanisms by which B cells accumulate in the sinonasal mucosa may therefore have significance in the pathogenesis of nasal polyposis. B-cell–activating factor of the TNF family (BAFF) has been identified to play an important role in B-cell survival, proliferation, and maturation, and levels of BAFF are significantly elevated in nasal polyp tissue compared with control tissues.9,10 Although local production of BAFF, and other factors such as IL-6, may expand or maintain the B cells that migrate to sinus tissue, very little information is available as to how B cells and their precursors are initially attracted to nasal tissue in patients with CRS.

Chemokines are a family of small cytokines 8–10 kDa in size that induce chemotaxis of motile cells including B cells. Elevated levels of various chemokines in nasal polyp tissue (e.g., the C-C chemokine RANTES) are already believed to promote local chemotaxis of T cells and eosinophils in CRSwNPs.11–13 The current study assessed levels of four B cell attracting chemokines in nasal polyp and control tissues: B-cell attracting chemokine 1 (CXCL13/BCA-1/BLC), thymus expressed chemokine (CCL25/TECK), mucosae-associated epithelial chemokine (CCL28/MEC), and stromal cell–derived factor 1α (CXCL12/SDF-1α). Each of these chemokines has been shown to recruit B cells or IgA+ plasmablasts in studies in mice and humans.14–16 Chemokine levels were measured by ELISA of tissue homogenates. In a second set of experiments, quantitative real-time polymerase chain reaction (PCR) was performed on cDNA from additional sinus tissue samples to detect the presence of mRNA for selected chemokine and chemokine receptor genes. The present investigation is an extension of an earlier preliminary report.17

MATERIALS AND METHODS

Study Design

BCA-1, TECK, MEC, and SDF-1α were assayed and levels in polyp samples from CRSwNP patients and inferior turbinate samples from CRSwNP patients, CRSsNP patients, and normal controls were compared. Concentrations of each chemokine in tissue homogenates were determined using ELISA. A panel of additional tissue specimens was evaluated by real-time PCR using specific primers to quantify mRNA levels of relevant chemokine receptor genes, as well as BCA-1 and CD20.

Subjects and Specimens

Subjects with CRSwNPs or CRSsNPs or controls with no evidence of CRS were invited to participate in the study. Each patient gave informed consent, and the study was approved by the Institutional Review Board at Northwestern University. The diagnosis of CRSwNPs or CRSsNPs in this study was based on clinical criteria defined by a recent expert consensus panel and confirmed by office endoscopy and computed tomography (CT) imaging.1 All CRS patients undergoing endoscopic sinus surgery had previously failed adequate trials of maximal medical therapy including prolonged antibiotic regimens, nasal steroid sprays, oral steroids, saline irrigations, and decongestants.

The population was limited to otherwise healthy adults between the ages of 18 and 70 years. Subjects taking anticoagulants, who have received an organ transplant, who have taken oral corticosteroids or antibiotics within the previous 2 weeks, or who have a confounding concomitant disease such as sarcoidosis or immunodeficiency were excluded from the study. Additional exclusion criteria included patients with antrochoanal polyps, cystic fibrosis, allergic fungal sinusitis, or unilateral nasal polyps.

All tissue samples were obtained during planned endoscopic sinus surgery in patients with CRS. Control sinonasal tissue was obtained from patients without evidence of CRS, rhinitis, or asthma (normal patients) undergoing nasal and sinus surgery for noninflammatory disease such as septoplasty, rhinoplasty, fracture repair, or pituitary tumor surgery. The study samples for ELISA included CRSwNP polyp tissue (n = 17), CRSwNP inferior turbinate (n = 6), CRSsNP inferior turbinate (n = 8), and normal inferior turbinate (n = 6). Seven patients were diagnosed with allergic rhinitis by positive skin testing (three patients with CRSsNPs and four patients with CRSwNPs). Nine of the patients were noted to be on intranasal steroids at the time of specimen collection (three patients with CRSsNPs and six patients with CRSwNPs). Two patients were on antihistamines at the time of specimen collection, both of whom had CRSwNPs. Tissue samples included for analysis of mRNA were from a separate group of subjects and consisted of polyp tissue taken from CRSwNPs (n = 15), inferior turbinate tissue from CRSwNPs (n = 12), inferior turbinate tissue from patients with CRSsNPs (n = 9), and inferior turbinate tissue from normal controls (n = 12). Five patients were diagnosed with allergic rhinitis by positive skin testing (one patient with CRSsNPs and four patients with CRSwNPs). Fifteen patients were noted to be on intranasal steroids at the time of specimen collection (3 patients with CRSsNPs and 12 patients with CRSwNPs). Data regarding antihistamine use were not available in this subset.

Specimen Preparation and Assay

Preparation of Polyp/Sinus Tissue Extracts

Sinonasal surgical tissue samples were treated and proteins were extracted as described previously.9 Briefly, 100 mg of polyp or inferior turbinate tissue was suspended in 1 mL of PBS-Tween in the presence of a cocktail of protease inhibitors (Sigma Chemical Co., St. Louis, MO) added at a 1:100 dilution. The samples were then homogenized for ~1 minute on ice at 24,000 rpm with an Ultra-Turrax T8 Homogenizer (IKA Works, Inc., Wilmington, NC). The tissue suspension was allowed to settle for 30 minutes on ice. The suspensions were then centrifuged at 4000 rpm for 20 minutes at 4°C. The supernatants were collected and stored at −80°C until analysis. The protein concentrations for the extracts were determined by the Bradford method using a BIORAD protein assay kit (Bio-Rad, Hercules, CA).

ELISA

Before ELISA analysis, samples were thawed at room temperature and vortexed to ensure a well-mixed sample. Chemokines were assayed using commercially available assay kits (R&D, Minneapolis, MN). The color intensity was measured using MicroPlate Reader Software applied to the sandwich enzyme immunoassay technique. Concentrations of chemokines in the tissue homogenate were normalized to the concentration of total protein. The minimum detectable concentration was 1.64 pg/mL for human BCA-1, 16 pg/mL for SDF-1α, and 62.5 pg/mL for TECK and MEC.

Real-Time PCR

Total RNA from sinus tissue was extracted using QIAzol (Qiagen, Valencia, CA) and was cleaned and treated with DNase I using RNeasy (Qiagen) according to the manufacturer’s instructions. Quality of total RNA from sinus tissue was assessed with a 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA) using a RNA 6000 Nano LabChip (Agilent Technologies). Single-strand cDNA was synthesized with SuperScript II reverse transcriptase (Invitrogen, Carlsbad, CA) and random primers. Semiquantitative real-time reverse-transcription (RT) PCR was performed with a TaqMan method using an Applied Biosystems 7500 Sequence Detection System (Applied Biosystems, Foster City, CA) as described previously. Primer and probe sets for five genes, CXCR4 (sense, 5′-CTGAGAAGCATGACGGACAAGTA-3′; antisense, 5′-CAGAAGGGAAGCGTGATGACA-3′; FAM/black hole quencher 1 [BHQ1] labeled probe, 5′-CTGTCAGTGGCCGACCTCCTCT-3′), CXCR7 (sense, 5′-CAACCTCTTCGGCAGCATTT-3′; antisense, 5′GGGTGTTGGTGAAGTAGGTGATG-3′; FAM/BHQ1 labeled probe, 5′-TGCATGAGCGTGGACCGCTACCT-3′), CXCR5 (sense, 5′-CTGGCGCAGGAGCAGTCT-3′; antisense, 5′-CCACGGTGAGCCCTTAGGA-3′; FAM/BHQ1 labeled probe, 5′-TCCCAGTGTCCCCTTTTATTGCTGCTTT-3′), BCA-1 (sense, 5′-GGACTCAGAGCTCAAGTCTGAACTC-3′; antisense, 5′-CAGCAGCATGAGAAGCAGAGA-3′; FAM/BHQ1 labeled probe, 5′-TCCAGACAGAATGAAGTTCATCTCGA-3′), and CD20 (sense, 5′-CACTCTTCAGGAGGATGTCTTCACT-3′; antisense, 5′-TCTGGACAGCCCCCAAAGT-3′; FAM/MGB labeled probe; 5′-TCTTCATGAGGGAATCTA-3′) were synthesized by Applied Biosystems or Integrated DNA Technologies (Coralville, IA). A primer and probe set for β-glucuronidase (human β-glucuronidase endogenous control, part number 4326320) was purchased from Applied Biosystems. To determine the exact copy number of the target genes, quantified aliquots of purified PCR fragments of the target genes were serially diluted and used as standards in each experiment. Aliquots of cDNA equivalent to 10 ng of total RNA were used for real-time PCR. The mRNA expression levels were normalized to the median expression of the housekeeping gene, β-glucuronidase.

Immunohistochemistry

The CD20 antibody used is a mouse monoclonal tissue culture supernatant, CD20 Ab-1 Clone L26 (Thermo Fisher Scientific, Fremont, CA). Three-micrometer sections of formalin-fixed, paraffin-embedded tissue from CRSwNP patients were incubated with CD20 antibody at a dilution of 1:250 overnight, for 16–20 hours, at 4°C. After rinsing, biotinylated horse anti-mouse secondary antibody (Vector Laboratories, Burlingame, CA) was used for 1 hour at room temperature, at a dilution of 1:500. After a second rinsing, sections were incubated with avidin-peroxidase complex (Vectastain Elite ABC Kit; Vector Laboratories) for 1 hour at room temperature. After a third rinsing, sections were incubated with diaminobenzidine chromogen (Invitrogen, South San Francisco, CA) for 10 minutes. Counterstaining with Gill modified hematoxylin (EMD Chemicals, Durmstadt, Germany) was done for 5–10 seconds. Sections were dehydrated, cleared, and mounted, and photographs were then taken using a MicroFire AR digital microscope camera (Optronics, Goleta, CA). Supernatant, clone L26, was run at a dilution of 1:250.

Data Analysis

Comparisons between groups were made using the Mann-Whitney U test on Prism Version 4 (GraphPad Software, Inc., La Jolla, CA). A value of p < 0.05 was considered significant. Correlations were assessed using the Spearman’s rank correlation. A value of p < 0.05 was considered significant. Use of nasal steroids or presence of positive skin testing was not significantly associated with alterations of either ELISA or RT-PCR findings (not shown).

RESULTS

Enzyme-Linked Immunosorbent Assay

Extracts from a total of 37 sinonasal surgical samples were processed for ELISA, which was performed for each of the four chemokines studied. The patients’ ages ranged from 25 to 74 years, with a mean age of 43 ± 12 years, with 11 total female patients and 26 male patients (Table 1). SDF-1α was prominently expressed in polyp tissue as shown in Fig. 1 A. SDF-1α was never detected in extracts of inferior turbinate tissues from CRSsNP patients and controls. This difference in expression between CRSwNP samples and turbinate samples from normal and CRSsNPs and CRSwNPs was statistically significant with values of p = 0.01 or less for each comparison. As shown in Fig. 1 B, levels of expression of BCA-1 were dramatically increased in polyp tissue compared with turbinate tissue from CRSwNP patients, CRSs-NPs, and controls. Compared with normal tissue, levels of BCA-1 were elevated over 20-fold. Statistical evaluation indicated that polyp tissue manifested significantly higher levels of BCA-1 compared with turbinate tissue from control and CRSsNP patients (p < 0.05 in each case) but not turbinate tissue from CRSwNP patients (p = 0.08). TECK expression displayed considerable variability and there were no significant differences between groups regarding levels of this chemokine (Fig. 1 C). Levels of MEC expression also displayed variability and were significantly lower in inferior turbinate tissue from CRSsNP patients (Fig. 1 D). This finding was recently confirmed in a microarray study of CRS (not shown).

Table 1.

Subject characteristics

Sample Type ELISA Studies RT-PCR Studies
Age Median (range; yr) Gender Age Median (range; yr) Gender
Normal IT 38 (31–59) 1 female, 5 males 36 (20–77) 2 females, 10 males
CRSsNP IT 44 (25–64) 5 females, 3 males 34 (27–55) 6 females, 6 males
CRSwNP IT 32 (27–54) 2 females, 4 males 44 (28–69) 5 females, 4 males
CRSwNP polyp 44 (28–74) 3 females, 14 males 44 (28–74) 5 females, 10 males
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IT = inferior turbinate; CRSsNP = chronic rhinosinusitis without nasal polyp; CRSwNP = chronic rhinosinusitis with nasal polyp; RT-PCR = reverse-transcription polymerase chain reaction‥

Figure 1.

Figure 1

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The concentration of (A) SDF-1α, (B) BCA-1, (C) TECK, and (D) MEC in tissue homogenates of inferior turbinate and polyp samples was measured using ELISA. Concentration was normalized to the concentration of total protein. Levels of both SDF-1α and BCA-1 were significantly different between CRSwNP polyp tissue and samples from CRSsNP as well as normals. Normal IT = inferior turbinate tissue from control patients; CRSsNP IT = inferior turbinate tissue from chronic rhinosinusitis without nasal polyp patients; CRSwNP IT = inferior turbinate tissue from chronic rhinosinusitis with nasal polyp patients; CRSwNP polyp = polyp tissue from chronic rhinosinusitis with nasal polyp patients; SDF = stromal cell–derived factor; BCA = B-cell attracting chemokines; TECK = thymus expressed chemokine; MEC = mucosae-associated epithelial chemokine.

Real-Time PCR

Extracts from a total of 48 sinonasal surgical samples were processed for quantitative real-time PCR for receptors for SDF-1α (CXCR4 and CXCR7) and BCA-1 (CXCR5), as well as BCA-1 itself. The patients’ ages ranged from 20 to 77 years, with a mean age of 39 ± 9 years, with 18 total female patients and 30 male patients (Table 1). Levels of mRNA for CD20 were also assayed from polyp tissue. Significantly increased levels of CXCR4 (Fig. 2 A) and CXCR7 (Fig. 2 B) mRNA were shown in polyp tissue when compared with tissue samples from controls and CRSsNP patients, as well as turbinate tissue from CRSwNP patients (p < 0.02 for all associations). Levels of CXCR5 mRNA exhibited a trend toward increased expression in polyp tissue, but this did not reach significance (Fig. 2 C). Levels of BCA-1 mRNA, however, were elevated in polyp tissue when compared with tissue samples from controls and CRSsNP patients (p < 0.05 for both; Fig. 3 A). Furthermore, BCA-1 mRNA levels were found to positively correlate with mRNA levels of its receptor CXCR5 (r = 0.56 and p < 0.0001; Fig. 3 B), as well as mRNA levels of the B-cell marker CD20 (r = 0.64 and p < 0.0001; Fig. 3 C).

Figure 2.

Figure 2

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Total RNA was extracted from polyps and from turbinate tissue in patients with CRSwNPs, CRSsNPs, and CRS-free controls and was analyzed by RT-PCR. (A) CXCR4 and (B) CXCR7 mRNA levels were significantly elevated in polyps compared with all other tissue types. (C) CXCR5 mRNA levels were also elevated in polyp tissue but this was not statistically significant. CRSwNPs = chronic rhinosinusitis with nasal polyps; CRSsNPs = chronic rhinosinusitis without nasal polyps; RT-PCR = reverse-transcription polymerase chain reaction.

Figure 3.

Figure 3

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Levels of BCA-1, CD20, and CXCR5 mRNA were analyzed by RT-PCR in the indicated samples; (A) BCA-1 mRNA levels were significantly elevated in polyps compared with tissue from CRSsNP patients and normal controls. BCA-1 mRNA levels also positively correlated with mRNA levels for (B) CXCR5 and (C) CD20, and both of these associations were statistically significant. BCA = B-cell attracting chemokines; RT-PCR = reverse-transcription polymerase chain reaction; CRSsNPs = chronic rhinosinusitis without nasal polyps.

DISCUSSION

The goal of this study was to determine the presence of B-cell chemoattractant chemokines that may contribute to the accumulation of B lymphocytes and plasma cells observed in sinonasal tissues of patients with CRS. We performed ELISA assays on detergent extracts of tissue taken from patients and controls during sinus surgery to evaluate expression of four chemokines known to recruit B cells based on studies in mice and humans. The results from the study show that SDF-1α and BCA-1, but not TECK or MEC, were elevated in nasal polyp tissue and thus may play a role in B-cell recruitment to nasal polyp tissue. Follow-up examination of mRNA levels revealed that receptors for SDF-1α (CXCR4 and CXCR7) and BCA-1 (CXCR5) were also up-regulated in polyp tissue, further implicating a role for these chemokines in CRSwNPs. At last, the present report also shows a positive correlation between BCA-1 mRNA and B-cell populations in polyp tissue, as reflected by CD20 mRNA.

A specific role for the observed elevations of SDF-1α in the development of nasal polyposis is uncertain at present, but this chemokine activates migration through CXCR4 and is known to contribute to B-cell trafficking. Other investigators have observed CXCR4 mRNA to be significantly elevated in the nasal tissue of symptomatic allergic rhinitis patients when compared with normal subjects.18 A bradykinin challenge was also noted to significantly increase CXCR4 mRNA levels in nasal tissue of mild allergic rhinitis patients when compared with normal subjects.18 The present data complement the aforementioned observations by showing significant elevations of both CXCR4 mRNA and the CXCR4 ligand SDF-1α in polyp tissue samples. Moreover, mRNA of a recently established alternate receptor for SDF-1α, CXCR7, was also significantly elevated in polyp tissue samples. SDF-1α is also a potent and effective factor for the recruitment of stem cells and is thought to play a role in tissue regenerative responses.19 The present observation of elevated SDF-1α may therefore also reflect an ongoing regenerative response.

BCA-1 is mainly produced by reticular cells, such as follicular dendritic cells. Others have also recently suggested a potential role for this chemokine in CRS using microarray analysis. These authors observed greater than a fivefold up-regulation of BCA-1 gene expression in sinus mucosa of children with CRS compared with controls, supporting the present findings that increased BCA-1 protein levels were evident in polyp tissue.20 This chemokine has been reported to attract CXCR5+ cells to B-cell follicles in lymphoid tissues. Naive B cells are known to be CXCR5+ and migrate to lymph nodes mainly via modified high endothelial venules, which present BCA-1 juxtaposed to, or inside of, the lymphoid follicle. These naive B cells are next attracted to the mantle zone where BCA-1 is released from dendritic elements such as the follicular dendritic cell tips. During embryogenesis, CXCL13 plays a key role in the recruitment of lymphoid tissue inducer cells, which initiate the formation and organization of lymphoid organs, such as lymph nodes and Peyer’s patches. BCA-1 and CXCR5 are expressed in normal human gut–associated lymphoid tissue structures, both in the ileum and colon, as well as in irregular lymphoid aggregates of inflammatory bowel disease lesions. It has also been found that the induction of BCA-1 expression is one of the strongest correlates for the development of ectopic lymphoid follicles in rheumatoid joints. The overexpression of BCA-1 at ectopic sites, such as the pancreas, is sufficient to drive the development of ectopic lymphoid follicles with B cells, follicular dendritic cells, and high endothelial venules.21

Another recent study has noted that inducible bronchus-associated lymphoid tissue, which is most prevalent in patients with pulmonary complications of autoimmune diseases such as rheumatoid arthritis and Sjogren’s syndrome, consists of numerous B-cell follicles containing germinal centers and follicular dendritic cells. Interestingly, expression of lymphoid-organizing chemokines, such as BCA-1, and also BAFF, correlated with an increased number and structural complexity of inducible bronchus-associated lymphoid tissue areas in the lung.22 Although there are no formal reports of the formation of isolated lymphoid follicles in CRS, we and others have observed foci of lymphoid neogenesis to be present in polyp tissue in the patients with CRSwNPs (Fig. 4); thus it is possible that one role of BCA-1 is to recruit and capture B cells that are attracted to the sinuses in isolated follicles. It is interesting to note that specialized B helper T cells that reside in follicles and are important in their formation are also attracted by BCA-1 and migrate via the actions of CXCR5.23

Figure 4.

Figure 4

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The figure represents a 3-µm-thick section of sinonasal mucosa derived from a patient with CRSwNP, revealing a prominent cluster of CD20+ cells, indicative of a B-cell follicle. CRSwNPs = chronic rhinosinusitis with nasal polyps.

Because B-cell production of IgA and IgE in nasal polyp tissue may play a role in local inflammation, chemokines that attract B cells may have significant relevance to the pathogenesis of CRSwNPs.4,7 Taken together, the present data suggest that SDF-1α and BCA-1 may play roles in the recruitment and retention of B cells in the tissues of patients with CRSwNPs. Additionally, our previous data have revealed that IgA levels were three- to sixfold higher in polyp extracts than in tissue extracts from other groups, further implicating a significant role for B cells in the pathogenesis of CRSwNPs.4 Investigations are underway to elucidate whether these chemokines recruit progenitor cells that then differentiate, proliferate, and reside in the tissue or recruit mature cells to sites of the inflammation in the sinuses and upper airways. Additional studies will attempt to correlate expression of B-cell chemokines with lymphoid follicular development and antibody production in polyp tissue.

Acknowledgments

Support for the conduct of the study and preparation of the article was provided by an American Rhinologic Society CORE Grant, grants R01 HL068546, R01 HL078860, and R01 AI072570, from the National Institutes of Health and the Ernest S. Bazley Trust

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