Basophils and eosinophils in allergic rhinitis
1994; Elsevier BV; Volume: 94; Issue: 6 Linguagem: Inglês
10.1016/0091-6749(94)90346-8
ISSN1097-6825
AutoresRobert M. Naclerio, Fuad M. Baroody, Anne Kagey‐Sobotka, Lawrence M. Lichtenstein,
Tópico(s)Mast cells and histamine
ResumoUnequivocal data support the role of the mast cell in the immediate or early-phase anaphylactoid reaction to antigen. Although the contribution of the early reaction to the pathophysiology of allergic rhinitis should not be ignored, there is clear evidence that the early response cannot fully explain the extent of the disease. One of the more important observations that led investigators to this conclusion is that systemic corticosteroids do not inhibit the early response to antigen in the nose, despite having a profound effect on the clinical course of the disease.1Pipkorn U Proud D Lichtenstein LM et al.Effect of short-term systemic glucocorticoid treatment on human nasal mediator release after antigen challenge.J Clin Invest. 1987; 80: 957-961Crossref PubMed Scopus (129) Google Scholar This discrepancy in the effect of systemic corticosteroids between experimental and clinical disease led to multiple investigations into the inflammatory processes after the early reaction. The central hypothesis behind these efforts was that the infiltration of inflammatory cells into the site of an allergic reaction alters the reactivity of the end organ. In the nose, manifestations of altered reactivity include late-phase reactions, priming, and hyperresponsiveness to nonantigenic stimuli. We briefly describe here some of our observations on the characterization of the cellular changes that occur after nasal provocation with antigen. We will not only focus on changes in basophils and eosinophils in nasal secretions but also include some observations on cellular changes that occur within the nasal mucosa.BASOPHILSIn human nasal provocation studies levels of both histamine and prostaglandin D2 (PGD2) increased in nasal lavages during the early reaction to allergen challenge, but only histamine increased during the late reaction.2Naclerio RM Proud D Togias AG et al.Inflammatory mediators in late antigen-induced rhinitis.N Engl J Med. 1985; 313: 65-70Crossref PubMed Scopus (584) Google Scholar Because mast cells and basophils both contain histamine but only mast cells, not basophils, can generate PGD2,3MacGlashan Jr, DW Schleimer RP Peters SP et al.Comparative studies of baosphils and mast cells.Fed Proc. 1983; 42: 2504PubMed Google Scholar we hypothesized that mast cells were the source of histamine during the early reaction whereas basophils were the source during the late reaction. To support this hypothesis we used light-microscopic criteria and alcian blue staining to identify basophils in nasal secretions during the late reaction (Fig. 1). We found a strong correlation between the influx of basophils during the late-phase reaction and the concurrent late increase in histamine (r = 0.72; p < 0.001).4Bascom R Wachs M Naclerio RM Pipkorn U Galli SJ Lichtenstein LM Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment.J ALLERGY CLIN IMMUNOL. 1988; 81: 580-589Abstract Full Text PDF PubMed Scopus (184) Google Scholar Because basophils made up approximately 1% of the cell influx, their numbers were too small to allow the use of electron microscopy for more definitive identification. Therefore we tried to study the functional characteristics of these cells ex vivo in an attempt to confirm our hypothesis.We challenged allergic subjects with antigen and recovered cells from their nasal secretions 24 hours later.5Iliopoulos O Baroody F Naclerio RM Bochner BS Kagey-Sobotka A Lichtenstein LM Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils.J Immunol. 1992; 148: 2223-2228PubMed Google Scholar We examined the ability of these cells to release histamine in response to a number of stimuli. Before any stimulation, the cells had a high degree of spontaneous histamine release. However, they responded to N-formyl-methionyl-leucyl-phenylalanine, a secretagogue that preferentially stimulates basophils but not mast cells (Fig. 2). They also responded to anti-IgE in a dose-dependent fashion, and the highest histamine release occurred at 0.1 μg/ml of anti-IgE, a dose that also leads to maximal release from blood basophils6Marone G Kagey-Sobotka A Lichtenstein LM IgE-mediated histamine release from human basophils: differences between antigen E and anti-IgE-induced secretion.Int Arch Allergy Appl Immunol. 1981; 65: 339-343Crossref PubMed Scopus (54) Google Scholar (Fig. 2). On the other hand, maximal histamine release from lung mast cells occurs at anti-IgE concentrations between 1 and 3 μg/ml.7Schulman ES MacGlashan Jr, DW Peters SP Schleimer RP Newball HH Lichtenstein LM Human lung mast cells: purification and characterization.J Immunol. 1982; 129: 2662-2667PubMed Google Scholar Nasal cells also released histamine in response to ragweed Amba I.5Iliopoulos O Baroody F Naclerio RM Bochner BS Kagey-Sobotka A Lichtenstein LM Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils.J Immunol. 1992; 148: 2223-2228PubMed Google Scholar These studies demonstrated that the functional characteristics of nasal leukocytes were those of basophils, not mast cells.FIG. 2Nasal leukocyte histamine release in response to different stimuli. Data are depicted as mean ± SEM of seven experiments. Nasal leukocytes released histamine in a dose-dependent fashion in response to anti-IgE and also responded to N-formyl-methionyl-leucyl-phenylalanine (FMLP). (From Iliopoulos O, Baroody F, Naclerio RM, Bochner BS, Kagey-Sobotka A, Lichtenstein LM, J Immunol 1992;148:2223-8. Copyright 1992, The Journal of Immunology.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)We further attempted to characterize these histamine-secreting cells by evaluating them for surface markers with indirect immunofluorescence and flow cytometry. Cells obtained 24 hours after antigen provocation were double stained for IgE and CD18, a surface marker present on basophils but not on mast cells.8Valent P Ashman LK Hinterberger W et al.Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes.Blood. 1989; 73: 1778-1785Crossref PubMed Google Scholar, 10Rimmer EF Horton MA Mast cells form a unique hemapoietic lineage.in: Leukocyte typing III: white cell differentiation antigens. : Oxford University Press, Oxford1988: 729-731Google Scholar More than 90% of IgE-bearing cells were also found to coexpress CD18 (Fig. 3), further evidence that cells entering the nasal secretions during the late reaction were basophils.5Iliopoulos O Baroody F Naclerio RM Bochner BS Kagey-Sobotka A Lichtenstein LM Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils.J Immunol. 1992; 148: 2223-2228PubMed Google ScholarFIG. 3Coexpression of CD18 on IgE-bearing nasal leukocytes recovered by nasal lavages of allergic volunteers 24 hours after allergen provocation. Coexpression of CD18 was analyzed after initial gating with scatter, and green fluorescence was done to identify uniform population of IgE-bearing cells. Shaded and solid lines delineate areas that represent staining with control and CD18 antibodies, respectively. Region to left of arrow represents 95% of all control events. Data from one experiment are representative of three others. (From Iliopoulos O, Baroody F, Naclerio RM, Bcohner BS, Kagey-Sobotka A, Lichtenstein LM. J Immunol 1992;148:2223-8. Copyright 1992, The Journal of Immunology.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)The different pattern of mediator release between the early and late reaction suggested that mast cells did not participate in the late reaction. We tested this hypothesis further by evaluating nasal secretions for tryptase and 9α, 11β PGF2. The former is a specific marker for mast cells and not basophils, whereas the latter is the major metabolite of PGD2 and can thus provide information on whether PGD2 is synthesized but then rapidly metabolized, resulting in our inability to detect it during late-phase reactions. We studied seven subjects who had a late histamine response to nasal provocation with antigen. In these experiments striking increases in tryptase, PGD2 and 9α, 11β PGF2 were associated with the release of histamine during the early but not the late reaction (Fig. 4).11Naclerio RM, Hubbard W, Lichtenstein LM, Kagey-Sobotka A, Proud D. Histamine released during the nasal late phase reaction does not originate from mast cells. J ALLERGY CLIN IMMUNOL (in press).Google Scholar This study supports the role of the basophil in the late reaction and suggests that mast cells are not activated during the late reaction. This latter observation could have been determined only by lavage studies because biopsies would not distinguish the time at which mast cells were degranulated.FIG. 4Mediator release after nasal allergen challenge of allergic subjects. Data are depicted as mean ± SEM of seven subjects. Challenge protocol is shown on abscissa. Dil, diluent; 10, 100, and 1000; doses of antigen in protein nitrogen units; PW, wash 20 minutes after challenge with highest antigen dose. Dashed line separates early and late reactions.View Large Image Figure ViewerDownload Hi-res image Download (PPT)In addition to relating basophils to histamine release during the late reaction, we also investigated their relationship to hyperresponsiveness. In a study of nasal priming (defined as the increased reactivity to antigen subsequent to prior antigen stimulation) we found that the number of basophils increased on the days when priming occurred.12Wachs M Proud D Lichtenstein LM Kagey-Sobotka A Norman PS Naclerio RM Observations on the pathogenesis of nasal priming.J ALLERGY CLIN IMMUNOL. 1989; 84: 492-501Abstract Full Text PDF PubMed Scopus (78) Google Scholar Because our ex vivo studies showed that basophils obtained from nasal secretions released histamine in a dose-dependent manner in response to Amba I, it is reasonable to speculate that these cells may be a target for repeated antigen exposure in the nasal mucosa. Supporting this notion is the observation that rechallenge of the nasal mucosa 11 hours after an initial challenge leads to augmented histamine release without an augmentation in the release of PGD2.1Pipkorn U Proud D Lichtenstein LM et al.Effect of short-term systemic glucocorticoid treatment on human nasal mediator release after antigen challenge.J Clin Invest. 1987; 80: 957-961Crossref PubMed Scopus (129) Google Scholar This study suggests that the histamine obtained during the rechallenge response originates not only from the acute degranulation of mast cells but also from basophils that have been recruited during the late-phase reaction. Interestingly this increase in histamine on rechallenge with antigen is reduced by treatment with systemic steroids.1Pipkorn U Proud D Lichtenstein LM et al.Effect of short-term systemic glucocorticoid treatment on human nasal mediator release after antigen challenge.J Clin Invest. 1987; 80: 957-961Crossref PubMed Scopus (129) Google Scholar Basophil numbers also increase when the nose becomes hyperresponsive to histamine, an example of increased nonspecific reactivity.13Walden SM Proud D Lichtenstein LM Kagey-Sobotka A Naclerio RM Antigen-provoked increase in histamine reactivity: observations on mechanisms.Am Rev Respir Dis. 1991; 143: 642-648Crossref Google ScholarBasophils might have roles other than generation of histamine during the late-phase response, and among these could be the release of proinflammatory cytokines. Recent in vitro experiments with peripheral blood basophils have shown that these cells are capable of producing interleukin (IL)-4 in response to an IgE-mediated stimulus such as anti-IgE. The importance of this observation is evident because IL-4 is a mast cell growth factor14Saito H Hatake K Dvorak AM et al.Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interluekins.Proc Natl Acad Sci USA. 1988; 85: 2288-2292Crossref PubMed Scopus (252) Google Scholar and also promotes the switching of B cells to the production of IgE.15Del Prete G Maggi E Parronchi P et al.IL-4 is an essential co-factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants.J Immunol. 1988; 140: 4193-4198PubMed Google ScholarEOSINOPHILSThe presence of basophils in nasal secretions has been a focus of our studies. We recognize, however, that the cells entering the nasal lumen in greatest numbers are neutrophils and eosinophils.16Bascom R Pipkorn U Lichtenstein LM Naclerio RM The influx of inflammatory cells into nasal wasings during the late response to antigen challenge: effect of systemic steroid pretreatment.Am Rev Respir Dis. 1988; 138: 406-412Crossref PubMed Scopus (261) Google Scholar The eosinophil not only enters the nasal cavity hours after nasal provocation but also degranulates, as evidenced by the recovery of major basic protein in nasal lavage fluids.17Bascom R Pipkorn U Proud D et al.Major basic protein and eosinophil-derived neurotoxin concentrations in nasal lavage fluid after antigen challenge: effect of systemic corticosteroids and relationship to eosinophil influx.J ALLERGY CLIN IMMUNOL. 1989; 84: 338-346Abstract Full Text PDF PubMed Scopus (79) Google Scholar Multiple other lines of evidence support the eosinophil's functional role in allergic inflammation, but these are beyond the scope of this review. Instead, studies relating to the eosinophil in the nasal mucosa are discussed.We developed a localized nasal challenge system that allows us to perform biopsies at the site of challenge and at distant sites. To understand better the relationship between changes in cell number in nasal secretions and in the nasal mucosa after antigen challenge, we obtained nasal lavage and biopsy specimens from 18 allergic and 11 nonallergic subjects.18Lim MC, Taylor RM, Naclerio RM. The histology of allergic rhinitis and its comparison to nasal lavage. Am J Respir Crit Care Med (in press).Google Scholar We assessed biopsy specimens 24 hours after antigen challenge for mucosal thickening, intraepithelial migration of inflammatory cells, density of goblet cells and mucoserous glands, and thickness of basement membrane and subepithelial collagen deposition, and compared allergic and nonallergic subjects. The numbers of eosinophils, mononuclear cells, and neutrophils in lavages were also quantified. In 10 subjects we also obtained biopsy specimens 24 hours after allergen provocation from the challenged inferior turbinate (ipsilateral) and from the opposite unchallenged turbinate (contralateral).No significant differences were found in the numbers of goblet cells and glands or in basement membrane thickness and subepithelial collagen between the groups. Allergic subjects had significantly thicker epithelium than did nonallergic subjects (0.04 ± 0.004 mm vs 0.07 ± 0.01 mm; p < 0.01). Counts of intraepithelial mononuclear cells were significantly higher in allergic versus nonallergic subjects (56 ± 4 cells/mm2 vs 39 ± 7 cells/mm2; p < 0.05). These differences between the allergic and nonallergic subjects were observed on examination of both the ipsilateral and contralateral biopsy specimens of the allergic subjects, suggesting that the increases in intraepithelial mononuclear cells and the thickening of the basement membrane are preexisting conditions in allergic subjects. When compared with nonallergic subjects, allergic subjects had significantly more eosinophils and neutrophils in lavage and more eosinophils and mononuclear cells in the nasal mucosa (Fig. 5). A significant increase in tissue eosinophils and mononuclear cells occurred only at the site of challenge. The increase in eosinophil count did not affect the histologic appearance of the epithelium, because the epithelial thickness was similar at the site of challenge and in the opposite nostril. This finding contrasts with the idea that eosinophil influx leads to epithelial desquamation during the late-phase reaction.FIG. 5Eosinophil count in nasal biopsy specimens from allergic and nonallergic subjects. Data are depicted as mean ± SEM. Ipsi, Specimens obtained at ipsilateral (same) site of allergen challenge in allergic subjects out of season; Contra, specimens obtained from contralateral unchallenged site in same allergic subjects; Diluent, specimens obtained from seasonal allergic subjects out of season, 24 hours after challenge with diluent for allergen extract; Control, specimens from nonallergic subjects 24 hours after ragweed allergen challenge. Asterisk, p < 0.05 versus all other groups.View Large Image Figure ViewerDownload Hi-res image Download (PPT)To identify the mononuclear cells in the nasal mucosa after allergen provocation, we challenged with ragweed extract 13 subjects with allergic rhinitis out of season.19Lim M Baroody FM Lee BJ Naclerio RM Taylor RM Nasal mucosa cellular changes after allergen challenge.J ALLERGY CLIN IMMUNOL. 1993; 91 ([Abstract]): 181Google Scholar Antigen was applied to one inferior turbinate, and biopsy specimens of both turbinates were obtained 24 hours later. Results of the ipsilateral biopsies were compared with those of the contralateral side and with biopsy results of the inferior turbinates of eight allergic subjects with rhinitis out of season without previous challenge. Immunostaining with the modified alkaline phosphatase/anti–alkaline phosphatase method was then performed. Monoclonal antibodies against CD3 (total T lymphocytes), CD4 (helper T cells), CD8 (suppressor T cells), CD25 (IL-2 receptor–bearing cells), CD19 (B cells), CD14 (monocytes), CD45 (leukocytes), and HLA-DR were used for staining. There were significant increases in the numbers of CD45+, CD3+, CD4+, and CD25+ cells in the allergic subjects at the site of challenge when compared with the contralateral side and with biopsy specimens obtained from allergic subjects without prior provocation. No significant differences were noted in the numbers of CD8+, CD19+, CD14+, or HLA-DR+ cells. From these studies we concluded that the majority of leukocytes infiltrating the submucosa were lymphocytes of the helper subset, a portion of which are activated as evidenced by IL-2–receptor expression (CD25).In contrast to the results obtained from nasal provocation studies, biopsy specimens obtained only from subjects preseasonally and postseasonally showed changes in tryptase-positive mast cells and activated eosinophils, whereas changes in lymphocyte numbers were not identified. We found a similar difference between provocation and natural exposure when we compared changes in the number of lymphocytes 24 hours after challenge with those of lymphocytes in biopsy specimens obtained from symptomatic unchallenged perennial allergic subjects.19Lim M Baroody FM Lee BJ Naclerio RM Taylor RM Nasal mucosa cellular changes after allergen challenge.J ALLERGY CLIN IMMUNOL. 1993; 91 ([Abstract]): 181Google Scholar The differences between provocation experiments and natural exposure may reflect dose and duration of antigen stimulation and the ability of provocation experiments to concentrate antigen placement at the site of biopsy. We need to extend our observations to other time points to determine better the kinetics of the lymphocytic response. Changes found at 24 hours may reflect changes early in the season, whereas changes days later may better mimic seasonal changes.Because we hypothesize that cellular infiltration is important in the events that occur hours after allergen provocation, such as hyperresponsiveness to antigen and histamine, we must understand how these cells arrive at the site of inflammation. An early step in the movement of cells from the peripheral blood involves adhesion between circulating leukocytes and the vascular endothelium. The recent availability of monoclonal antibodies directed toward adhesion molecules permits the investigation of eosinophil recruitment in vivo. In vitro evidence suggests that vascular cell adhesion molecule–1 (VCAM-1) may be responsible in part for the selective adherence of eosinophils to the endothelium20Bochner BS Luscinskus FW Gimbrone MA Lichtenstein LM Schleimer RP Adhesion of human basophils, eosinophils and neutrophils to IL-1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules.J Exp Med. 1991; 173: 1553-1557Crossref PubMed Scopus (577) Google Scholar whereas intercellular adhesion molecule–1 (ICAM-1) is more important in transmigration.21Ebisawa M Bochner BS Georas SN Schleimer RP Eosinophil transendothelial migration induced by cytokines.J Immunol. 1992; 149: 4021-4028PubMed Google Scholar VCAM-1 upregulation on nasal vascular endothelium has been reported in perennial allergic subjects.22Montefort A Feather IH Wilson SJ et al.The expression of leukocyte-endothelial adhesion molecules is increased in perennial allergic rhinitis.Am J Respir Cell Mol Biol. 1992; 7: 393-398Crossref PubMed Scopus (131) Google Scholar Further support arises from subjects with leukocyte adhesion molecule deficiency (absence of CD18/CD11 glycoprotein on circulating leukocytes), who cannot recruit neutrophils to areas of inflammation but who can recruit eosinophils and lymphocytes to these sites via VCAM-1.23Williams TJ Hellewell PG Adhesion cell molecules involved in the microvascular inflammatory response.Am Rev Respir Dis. 1992; 146: S45-S50Crossref PubMed Google Scholar In biopsy specimens obtained 24 hours after antigen challenge, VCAM-1 expression on the vascular endothelium increased significantly in allergic subjects (n = 10) when compared with normal control subjects (n = 13) (26.7% ± 5.6% vs 12.9% ±3.8%; p < 0.05) whereas ICAM-1 was constitutively expressed and E-selectin was increased only slightly24Lee BJ Naclerio RM Bochner BS Baroody FM Upregulation of vascular cell adhesion molecule-1 (VCAM-1) after nasal allergen (Ag) challenge.J ALLERGY CLIN IMMUNOL. 1994; 93 ([Abstract]): 183Google Scholar (Fig. 6). Together with endothelial adhesion molecule upregulation, significantly more eosinophils were found in the nasal mucosa of the allergic subjects as compared with the nonallergic control subjects. Because the counterligand for VCAM-1, very late antigen–4, is present on eosinophils and lymphocytes but not on neutrophils, VCAM-1 upregulation may contribute to the selective recruitment of eosinophils to the nasal mucosa after allergen provocation. The modest upregulation of E-selectin after allergen provocation can be explained by in vitro studies with human umbilical vein endothelial cells, which showed that E-selectin expression in response to tumor necrosis factor–α and IL-1 began 1 to 2 hours after exposure was maximal at 4 to 6 hours, and decreased markedly by 24 hours.25Bevilacqua MP Stengelin S Gimbrone Jr, MA Seed B Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins.Science. 1989; 243: 1160-1165Crossref PubMed Scopus (1660) Google Scholar, 26Pober JS Bevilacqua MP Mendrick DL Lapierre LA Fiers W Gimbrone MA Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells.J Immunol. 1986; 136: 1680-1687PubMed Google Scholar Although the upregulation of VCAM-1 may play a role in the recruitment of eosinophils, chemoattractants and growth factors undoubtedly also contribute to the selective recruitment of eosinophils.FIG. 6Expression of adhesion molecules on nasal vascular endothelium. Data represent percentage of total vessels (identified by staining with von Willebrand factor) that stained positive with each of adhesion molecules studied: VCAM-1, E-selectin, and ICAM-1. Data are depicted as mean ± SEM of 10 allergic subjects (dark bars) and 13 nonallergic control subjects (striped bars). Biopsies were performed 24 hours after allergen provocation in both groups. Asterisk, p < 0.05 when allergic subjects were compared with nonallergic control subjects.View Large Image Figure ViewerDownload Hi-res image Download (PPT)We have shown that the predominant cells in nasal lavage 24 hours after challenge are eosinophils and neutrophils whereas simultaneous biopsy specimens have shown that the predominant cell in the mucosa is the CD4+ lymphocyte. Therefore we wanted to know which compartment, the nasal secretions or the mucosa, was more important in the allergic process. We thus studied the effect of intranasal steroids on the early symptomatic response and on the cellular infiltration that occurs 24 hours after allergen provocation.27Driscoll PV Naclerio RM Baroody FM Intranasal corticosteroids (IC) reduce eosinophil (EOS) in nasal secretions but not in the submucosa after allergen (Ag) challenge.J ALLERGY CLIN IMMUNOL. 1994; 93 ([Abstract]): 216Google Scholar Previous studies indicated that intranasal steroids did not prevent the increase in eosinophil numbers in the nasal mucosa after allergen provocation but did affect their level of activation.28Lozewicz S Wang J Duddle J et al.Topical glucocorticoids inhibit activation by allergen in the upper respiratory tract.J ALLERGY CLIN IMMUNOL. 1992; 89: 951-957Abstract Full Text PDF PubMed Scopus (55) Google Scholar These results are in contrast to other reports showing that eosinophil levels in lavage are decreased.4Bascom R Wachs M Naclerio RM Pipkorn U Galli SJ Lichtenstein LM Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment.J ALLERGY CLIN IMMUNOL. 1988; 81: 580-589Abstract Full Text PDF PubMed Scopus (184) Google Scholar, 16Bascom R Pipkorn U Lichtenstein LM Naclerio RM The influx of inflammatory cells into nasal wasings during the late response to antigen challenge: effect of systemic steroid pretreatment.Am Rev Respir Dis. 1988; 138: 406-412Crossref PubMed Scopus (261) Google Scholar These disparities may reflect changes in compartmentalization of cells between the mucosa and secretions. For example, eosinophils expressing very late antigen–4 can bind to fibronectin in the extracellular matrix, and steroids might not affect this process. Alternatively the levels of cytokines that promote eosinophil survival may be altered. Preliminary results from our study showed that sneezing and secretion weights were significantly suppressed by intranasal steroids, suggesting an effect on the immediate reponse to allergen provocation.27Driscoll PV Naclerio RM Baroody FM Intranasal corticosteroids (IC) reduce eosinophil (EOS) in nasal secretions but not in the submucosa after allergen (Ag) challenge.J ALLERGY CLIN IMMUNOL. 1994; 93 ([Abstract]): 216Google Scholar In nasal secretions the number of eosinophils that appeared was significantly lower when the subjects were treated with intranasal steroids. In contrast to the secretions, there was no difference in the number of eosinophils in the nasal mucosa between the placebo-treated and steroid-treated groups. These results suggest an effect of steroids on the superficial compartment without an effect on the deeper tissues. Therefore many potential explanations exist for these results and further studies are needed to better understand our findings.In conclusion, both the eosinophil and the basophil participate in the response to nasal challenge with allergen. However, as we learn more about the pathophysiologic mechanisms of allergic inflammation, the role of these two cell types seems to become more, rather than less, complex. They are being found to secrete more and more mediators, and the location of release of these mediators may differ (e.g., nasal mucosa vs nasal secretions). Furthermore, it is clear from the literature that other inflammatory cells also contribute to the pathophysiology of allergic inflammation, and the consideration of all the possible interactions of these cells with the basophil and the eosinophil make the process even more complex. Unraveling the contribution of each cell type and the effects of the mediators it secretes will help to improve our understanding of how deposition of allergen molecules on the nasal mucosal surface of a sensitized person leads to the clinical manifestations of allergic rhinitis. Unequivocal data support the role of the mast cell in the immediate or early-phase anaphylactoid reaction to antigen. Although the contribution of the early reaction to the pathophysiology of allergic rhinitis should not be ignored, there is clear evidence that the early response cannot fully explain the extent of the disease. One of the more important observations that led investigators to this conclusion is that systemic corticosteroids do not inhibit the early response to antigen in the nose, despite having a profound effect on the clinical course of the disease.1Pipkorn U Proud D Lichtenstein LM et al.Effect o
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