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PubMed1986

Basophilic cell progenitors, nasal metachromatic cells, and peripheral blood basophils in ragweed-allergic patients.

Circulating hematopoietic progenitor cells giving rise to colonies containing basophilic cells (basophilic cell colony-forming units in culture [CFU-c]), nasal epithelial metachromatic cells (basophils and/or mast cells) (NMC), and blood basophils were enumerated before, during, and after a ragweed-pollen season in patients with ragweed hayfever and patients with perennial allergic rhinitis who were not ragweed allergic. In the patients with seasonal hay fever, the following was observed: basophilic cell CFU-c, measured as basophilic cell or histamine-containing colonies, were significantly reduced during the ragweed season compared to before (p less than 0.005) or after (p less than 0.025) the season in the ragweed-allergic group only. Conversely, peripheral blood basophils were higher during the ragweed season than before or after (p less than 0.001) in the ragweed-allergic group, whereas the number of NMC was higher during the season than before the season in this group (p less than 0.05). There were no such changes during the season in the group of patients with perennial allergic rhinitis. The observed seasonal changes in both NMC and circulating basophilic cell CFU-c are discussed in the context of lineage relationships among metachromatic cell types.

Basophils↗
PubMed2002

Regulation of human basophil adhesion to endothelium under flow conditions: Different very late antigen 4 regulation on umbilical cord blood-derived and peripheral blood basophils.

BACKGROUND: Although soluble mediators released by basophils in tissue sites contribute to the chronic injury that occurs in hypersensitivity diseases, only limited information is available about how circulating basophils are recruited to tissues. In particular, the interaction of basophils with endothelium under conditions that mimic physiologic flow has not been explored. OBJECTIVE: We sought to identify adhesion molecules regulating the attachment of human basophils to IL-4-activated human umbilical vein endothelial cells (HUVECs) under flow conditions. METHODS: A parallel-plate flow chamber and blocking mAbs were used to define the adhesion molecules involved in the interactions of peripheral blood basophils (PBBs) and cord blood-derived basophils (CBDBs) with IL-4-activated HUVECs and with Chinese hamster ovary (CHO) cell transfectants expressing specific adhesion molecules. A fluorescent ligand specific for very late antigen 4 (VLA-4) was used to directly examine the VLA-4 affinity state of basophils. RESULTS: Flowing PBBs and CBDBs attached to activated HUVECs and to CHO cells expressing P- or E-selectin. However, only CBDBs attached to vascular cell adhesion molecule 1 (VCAM-1)-transfected CHO cells under flow conditions. The attachment of CBDBs to CHO cells was blocked by mAbs directed against E-selectin, P-selectin, and VCAM-1, whereas attachment of PBBs was blocked by E-selectin and P-selectin mAbs. Activating VLA-4 with Mn(2+) on PBBs resulted in adhesion to the VCAM-1-transfected CHO cells, indicating that VLA-4 activity on PBBs can be regulated, at least in part, through affinity changes. The Mn(2+)-induced upregulation of basophil VLA-4 affinity was demonstrated directly by using a fluorescent ligand for VLA-4 and flow cytometry. CONCLUSIONS: The interaction of human CBDBs and PBBs with endothelium under flow conditions is mediated in part by both P- and E-selectin. VLA-4 additionally contributes to the adhesion of flowing CBDBs. However, the affinity of VLA-4 is too low to support the adhesion under flow conditions of unstimulated PBBs.

Animals↗
PubMed2003

Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgE-mediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3.

Recent data suggest that the statins, apart from their lipid-lowering activity, exhibit profound anti-inflammatory effects. Basophils are major proinflammatory effector cells in diverse pathologic reactions. We have examined the in vitro effects of five different statins on primary human basophils, their progenitors, and the basophil cell line KU-812. Preincubation of blood basophils with cerivastatin or atorvastatin (0.1-100 microM) for 24 h reduced their capacity to release histamine on immunoglobulin E (IgE)-dependent stimulation in a dose-dependent manner. These statins also inhibited IgE-dependent up-regulation of the basophil-activation antigen CD203c. Moreover, both statins suppressed interleukin-3-induced differentiation of basophils from their progenitors as well as (3)H-thymidine uptake in KU-812 cells. All inhibitory effects of cerivastatin and atorvastatin were reversed by mevalonic acid (200 microM). The other statins tested (lovastatin, simvastatin, pravastatin) did not show significant inhibitory effects on basophils. Together, these data identify cerivastatin and atorvastatin as novel inhibitors of growth and activation of human basophils.

Antigens, CD↗
PubMed1987

The role of basophils and mast cells in cutaneous basophil hypersensitivity reaction.

Basophils are the main cell component in cutaneous basophil hypersensitivity (CBH) reactions, but the role of basophils and the factors which gather them into CBH reaction sites are unknown. To investigate these problems, we induced CBH reactions in guinea pigs and observed basophils and mast cells in the skin reaction sites using light and electron microscopy. Basophils infiltrated into CBH reaction site appeared at 5 h after the challenge with antigen, increased till 48 h and decreased thereafter. On the other hand, the number of mast cells and their granules decreased after the challenge with antigen and reached a minimum at 48 h, but recovered at 96 h. The changes in the number of basophils and mast cells were complementary. This result suggested that the granules of mast cells may have a factor to gather basophils into the CBH skin reaction site. Furthermore, basophils infiltrated in the CBH reaction site were degranulated by the rechallenge with antigen, which was considered to be by an anaphylactic reaction.

Animals↗
PubMed1982

IgG1 antibody-dependent mediator release after passive systemic sensitization of basophils arriving at cutaneous basophil hypersensitivity reactions.

When antigen is injected into a 24-hr cutaneous basophil hypersensitivity (CBH) reaction of an actively sensitized guinea pig, local basophils degranulate and release histamine. This reaction is called cutaneous basophil anaphylaxis and may be antibody mediated. We now report passive sensitization of basophils at CBH sites by systemic transfer of anti-picryl immune serum. Keyhole limpet hemocyanin- (KLH) immunized animals were skin tested with KLH to elicit 24-hr CBH reactions at day 7. Anti-picryl serum was injected i.v. at various times. On day 7, blue dye was injected i.v., and then 24-hr CBH sites vs nearby normal skin were challenged with 0.1 microgram picryl-human serum albumin (Pic-HSA). An immediate increase in vascular permeability (blueing) was noted at normal skin sites due to systemic passive cutaneous anaphylaxis (PCA), and augmented blueing occurred at CBH sites compared with normal skin. Systemic passive sensitization of CBH sites occurred when antiserum was administered as little as 1 hr before challenge of CBH site. However, local administration of anti-picryl serum (as in a local PCA reaction) was not able to sensitize tissue basophils, whether antigen was administered locally or systemically. The serum factor that mediated cutaneous basophil anaphylaxis was heat-stable (56 degrees C X 4 hr) 7S IgG1 antibody. Electron microscopy of Pic-HSA-challenged CBH sites in animals that received IgG1 antibody showed that local basophils undergo anaphylactic degranulation by exocytosis. These studies suggest that basophils arriving at CBH reactions are sensitized for anaphylactic function by antibody that can be acquired in the circulation, but possibly not at the local site.

Animals↗
PubMed2001

Nerve growth factor or IL-3 induces more IL-13 production from basophils of allergic subjects than from basophils of nonallergic subjects.

BACKGROUND: Studies show that nerve growth factor (NGF) exhibits immunomodulatory activity. This neurotrophin is found at high levels in the serum of asthmatic individuals, is released during allergic reactions, and is reported to augment in vitro histamine and leukotriene C4 release by human basophils. OBJECTIVE: Because basophils represent a substantial source of IL-4 and IL-13, we tested the effects of NGF on the secretion of these cytokines by cells prepared from allergic subjects and cells prepared from nonallergic subjects. METHODS: Cytokine and histamine were measured in culture supernatants by ELISA and fluorimetry, respectively. Both real-time RT-PCR and conventional RT-PCR were used to measure IL-13 mRNA expression. NGF receptor expression was determined by 2-color flow cytometry. RESULTS: Basophil suspensions from allergic subjects secreted some 2.5-fold greater levels of IL-13 when cultured with NGF than did cells prepared from normal control subjects. Flow cytometry revealed no significant differences in TrkA receptors on basophils to explain these findings. The levels of IL-13 secreted by the 2 groups of donors also differed when cells were activated with IL-3 but not when they were activated with anti-IgE antibody. Both NGF and IL-3 failed to induce IL-13 in cell cultures depleted of basophils, suggesting that the measurable IL-13 was indeed basophil-derived. Real-time RT-PCR showed an average induction of IL-13 message above medium control that was 4.3 (+/- 1.7)-fold with NGF and 8.9 (+/- 3.7)-fold with IL-3. Finally, NGF priming resulted in a remarkable enhancement of IL-13 induced by anti-IgE. This was significantly greater than the priming observed for either the IL-4 or histamine when this stimulus was used. CONCLUSION: NGF (like IL-3) can both directly stimulate IL-13 secretion and modulate IgE-mediated responses in basophils. Its enhanced effect on cells from allergic individuals raises the importance of this cytokine in the pathogenesis of allergic disease.

Adjuvants, Immunologic↗
PubMed1984

Cutaneous basophil hypersensitivity to inhalant allergens in atopic dermatitis patients: elicitation of delayed responses containing basophils following local transfer of immune serum but not IgE antibody.

Inhalant allergens applied to the skin of sensitive atopic dermatitis patients by means of a modified patch test technique, induce acute eczematous lesions. These lesions contain basophils, eosinophils, mononuclear cells, and neutrophils and represent an example of human cutaneous basophil hypersensitivity. The role of IgE antibody in this eczematous reaction was studied by systemic and local passive transfer experiments. Plasma with high IgE antibody when infused into patients with hypogammaglobulinemia as part of their replacement treatment resulted, post infusion, in cutaneous mast cell and blood basophil sensitization as measured by quantitative skin testing and leukocyte histamine release. Subsequent patch tests on these patients using the house dust mite antigen, antigen P1, produced macroscopic erythematous responses containing mononuclear cells, and eosinophils but not basophils. Local transfer of atopic dermatitis serum with high IgE antibody produced weak macroscopic responses and in these lesions mononuclear cells and both basophils and eosinophils were present. The serum activity which allowed transfer of basophil and eosinophil recruitment was heat labile. Specifically purified antibody to the mite antigen P1 (containing IgE and IgG antibody), when transferred, allowed eosinophil but not basophil recruitment to patch test sites. These results suggest that while the allergen-induced patch test response may involve IgE antibodies, as well as the cells normally involved in delayed responses, another serum activity is also involved.

Adolescent↗
PubMed1994

In vitro basophil histamine-releasing activity of circulating IgG1 and IgG4 autoanti-IgE antibodies from asthma patients and the demonstration that anti-IgE modulates allergen-induced basophil activation.

In this study we have examined the relationship between the in vitro basophil histamine-releasing activity of human IgG anti-IgE, isolated as euglobulin fractions from sera of asthmatic patients, and its IgG1/IgG4 subclass distribution. In particular, we have investigated whether IgG anti-IgE modulates allergen-induced basophil activation. The study has revealed that only a small proportion of IgG anti-IgE samples triggered histamine release from basophils of an asthmatic individual (4/21; 19%), a hay fever sufferer (4/10; 40%) and a healthy person (7/21; 33%). The basophil histamine-releasing activity of IgG anti-IgE did not seem to be determined by the IgG1/IgG4 subclass composition of the IgG anti-IgE preparation used. Furthermore, we have demonstrated that autoanti-IgE antibodies modulate allergen-induced basophil histamine release. The three modulatory effects exerted by IgG anti-IgE antibodies on allergen-triggered basophil activation (i.e. additive, synergistic and blocking) were not dependent on the subclass nature of IgG anti-IgE or the use of histamine-releasing anti-IgE preparations. Our data suggest that IgG anti-IgE antibodies in asthma patients may consist of two functionally distinct subpopulations: those which up-regulate (pro-allergic) and those which down-regulate (anti-allergic) the allergic release of mediators from mast cells and basophils.

Allergens↗
PubMed2006

Enumeration and immunohistochemical characterisation of bone marrow basophils in myeloproliferative disorders using the basophil specific monoclonal antibody 2D7.

BACKGROUND: Basophils are highly specialised granulocytes that express a unique profile of antigens and increase in myeloproliferative disorders (MPD). In chronic myeloid leukaemia (CML), basophilia is a diagnostic and prognostic determinant. So far, however, no reliable approach for routine detection and enumeration of bone marrow basophils has become available. OBJECTIVE: To detect and enumerate basophils in bone marrow sections in patients with CML and other MPD. METHODS: The anti-basophil antibody 2D7 was applied to paraffin embedded bone marrow sections from normal/reactive subjects (n = 31), patients with CML (chronic phase, n = 37; accelerated phase, n = 9), and other MPD (chronic idiopathic myelofibrosis (CIMF), n = 20; polycythaemia vera (PV), n = 20; essential thrombocythaemia (ET), n = 20; indolent systemic mastocytosis (ISM), n = 7). RESULTS: As assessed by serial section staining, 2D7(+) cells were found to co-express myeloperoxidase, histidine decarboxylase, CD9, and CD43, but did not express B cell or T cell restricted antigens. 2D7(+) bone marrow cells were found to increase in CML compared with normal/reactive bone marrow and other MPD (median numbers of 2D7(+) cells/mm(2): CML, 33; normal/reactive bone marrow, 6; CIMF, 10; PV, 6; ET, 5; ISM, 3; p<0.05). The highest basophil counts were recorded in accelerated phase CML (115/mm(2)). CONCLUSIONS: A novel immunohistochemical procedure has been established for basophil detection in normal bone marrow and MPD. This approach should help in the quantification of bone marrow basophils at diagnosis and during anti-leukaemic treatment.

Adult↗
PubMed1986

Serum basophil-stimulating activity in the guinea-pig during induction of basophilic responses to ovalbumin and tick feeding.

We have described functional and biochemical characteristics of a distinct T-cell dependent guinea-pig basophil-stimulating factor (BSF), measured using a sensitive 7-day bone marrow culture assay, standardized with high-activity BSF present in serum-free splenic cell-conditioned medium (CM). In the present studies, the in vivo relevance of BSF was explored during protocols of induction of peripheral blood or tissue basophil responses to ovalbumin (OA) injection or Amblyomma americanum tick feeding. Pooled immune serum, taken from OA-injected inbred or outbred animals during induction of blood and marrow basophilia, contained an in vitro inhibitor to BSF at high concentrations and BSF-like activity at low concentrations; maximal stimulation of histamine synthesis by bone marrow cells in vitro was found in the presence of Day 4 OA-immune serum. In vivo studies in the OA model demonstrated maximal serum BSF-like activity at 48-72 hr before peak bone marrow basophil response, followed by a levelling off to 50% of maximum at 2 weeks. In the tick model, serum BSF-like activity was present in Day 8, but not Day 1, post-primary infection and was maximal at Day 3 post-secondary infection; post-primary Day 1 serum was inhibitory to basophil growth in vitro. These observations suggest that BSF regulates the appearance of basophils in response to antigen in vivo by an effect on basophil progenitors. The observations stress the potential application of guinea-pig models to understanding the regulation of basophil production in allergic disorders.

Animals↗
PubMed1983

Sensitization of circulating basophils in guinea pig recipients of passive transfer of cutaneous basophil hypersensitivity (CBH) with immune serum: antigen-specific histamine release in vitro.

An in vitro histamine release assay was used to test the hypothesis that passive sensitization of circulating basophils is associated with the activity of immune serum that transfer the ability to elicit cutaneous basophil hypersensitivity (CBH) reactions. Systemic i.v. transfer of several types of immune sera that mediate CBH also led to passive sensitization of circulating basophils for antigen-specific release of histamine in vitro. In addition, we found that immune serum passively sensitizes basophils in vitro. Thus immune sera had three activities that are probably interconnected: sera will 1) passively transfer CBH in vivo, 2) passively sensitize basophils in vivo, and 3) passively sensitize basophils in vitro. These results suggest that passive sensitization of circulating basophils by immune serum contributes to the mechanism by which antibodies transfer the ability to elicit CBH reactions.

Animals↗
PubMed1982

Anaphylactic degranulation of guinea pig basophilic leukocytes. II. Evidence for regranulation of mature basophils during recovery from degranulation in vitro.

Mature circulating granulocytes have been considered functionally end stage cells unable to reconstitute their specific cytoplasmic granules. We have reevaluated this assumption by studying guinea pig peripheral blood basophils maintained in vitro for periods up to 72 hours after anaphylactic degranulation. Guinea pig basophils degranulated in vitro by exposure to either specific antigen (sheep serum) or lectin (Concanavalin A) synthesized new cytoplasmic granules. This process was characterized by the appearance of abundant rough endoplasmic reticulum, activation of the Golgi zone, interiorization of plasma membrane, and successive formation of empty vacuoles, multivesicular bodies, immature granules, and, finally, typical mature basophil granules. Although basophil neogranulogenesis in vitro was similar in most respects to that occurring in the bone marrow, it differed significantly in that regranulating basophils retained the nuclear characteristics of mature granulocytes. New basophil granule formation was more prominent and developed earlier when sheep serum was employed as the degranulation stimulus. Cultures degranulated with Concanavalin A, and, less commonly, sheep serum, also contained small numbers of basoblasts, large bizarre basophils with immature nuclear and cytoplasmic features, cytoplasmic lipid droplets, and mature, immature, and fused granules. These cells may arise by a process analogous to lymphocytes blast transformation.

Anaphylaxis↗
PubMed1982

Prolonged reduction in basophil counts at cutaneous basophil hypersensitivity reaction sites challenged with antigen.

Previous studies have shown that injection of antigen into 24 hr cutaneous basophil hypersensitivity (CBH) reaction sites results in immediate degranulation of local basophils and release of mediators, such as histamine, that increase vascular permeability. In the current study, cell counts were made at these antigen-challenged CBH sites, 4, 8 and 24 hr later, and demonstrated a prolonged reduction of basophil numbers following antigen challenge. These results were interpreted to signify that mediators released by degranulating basophils led to inhibition of subsequent basophil accumulation. Local eosinophil infiltration was not inhibited, and in some cases was augmented. Local injection of histamine into CBH sites did not mimic the effect of antigen. It was concluded that one of the factors regulating accumulation of basophils at CBH sites was degranulation of basophils that had arrived previously.

Animals↗
PubMed1994

Secretion of IL-4 from human basophils. The relationship between IL-4 mRNA and protein in resting and stimulated basophils.

Purified human basophils have been examined for secretion of IL-4 protein and expression of IL-4 mRNA after stimulation with several secretagogues. In general, these studies used a 15-min preincubation with IL-3, before challenge with secretagogues. Under these conditions, IL-4 release averaged 30 pg/10(6) basophils (range 4-70) after challenge with anti-IgE Ab. FMLP and C5a led to somewhat lower levels of secretion. A direct comparison of basophils at 88 to 99% purity with basophils from the same preparations, but at lower purities, showed that the amount of IL-4 secretion was proportional to the purity of the basophils. The presence of mRNA for IL-4 (as determined by reverse transcriptase-PCR, competitive reverse transcriptase-PCR, or Northern blots) was also strictly related to the purity of the basophils. IL-4 mRNA was also found to be constitutively present and was increased after stimulation. The concentration of polyclonal anti-IgE Ab required for optimal IL-4 release was somewhat less than that required for optimal histamine release. IL-4 secretion was slower (t1/2 of 1.5 h) than histamine release and was inhibited by cycloheximide. In a final series of studies, we found that IL-3 was not required for IL-4 secretion; a short 15-min preincubation with IL-3 resulted in the same or slightly less IL-4 release than no treatment with IL-3. In contrast, an 18-h pretreatment with IL-3 resulted in a nearly tenfold increase in IL-4 secretion. We conclude that human basophils secrete IL-4 in response to several secretagogues and that IL-3 priming is not necessary to observe IL-4 secretion.

Base Sequence↗
PubMed1990

Enhancement of basophil histamine release by a human basophil-like cell promoting activity.

A basophil-like cell promoting activity (BaPA) is a lymphokine which has the ability to proliferate metachromatically staining cells in human bone marrow. We studied the effect of BaPA on histamine release from human peripheral basophils. BaPA did not directly induce histamine release from basophils. However BaPA ranging from 0.001 to 0.5 U/ml enhanced histamine release from basophils stimulated with anti-IgE, calcium ionophore A23187 or FMLP in a dose-dependent manner. On the basis of recent observations that in addition to their capacity for proliferating progenitor cells, colony-stimulating factors are capable of regulating functions of end-stage cells of the same lineage, this finding that BaPA is able to modulate a basophil function raises the possibility that BaPA also regulates progenitors of basophils.

Basophil Degranulation Test↗
PubMed1991

Human basophil releasability. VIII. Increased basophil releasability in patients with scleroderma.

We evaluated basophil releasability in 16 female patients with scleroderma (systemic sclerosis) and in 16 normal age- and sex-matched donors. Basophils from patients with scleroderma released significantly more histamine "spontaneously" than did those from normal donors (12.9 +/- 2.1% versus 4.5 +/- 0.7%; P less than 0.0005). Basophil reactivity (maximal percentage histamine release) to anti-IgE was higher in patients with scleroderma than in controls (57.0 +/- 7.5% versus 35.4 +/- 7.8%; P less than 0.05). Basophil sensitivity (the concentration of anti-IgE that causes 40% of maximal percentage histamine release) to anti-IgE in scleroderma patients was similar to that found in controls (4.6 +/- 2.8 x 10(-2) micrograms/ml versus 2.3 +/- 1.0 x 10(-1) micrograms/ml; P not significant). Scleroderma patients also showed enhanced releasability compared with that of the controls when challenged in vitro with interleukin-3 (8.3 +/- 1.7% versus 3.2 +/- 0.6%; P less than 0.01). Releasability induced by the formyl-containing tripeptide, f-met peptide, was significantly higher in the scleroderma patients than in the controls at the 2 lower concentrations used. No differences in basophil reactivity and sensitivity to f-met peptide and calcium ionophore A23187 were found between patients and normal donors. These results show that spontaneous basophil releasability and releasability in response to IgE cross-linking and activation of interleukin-3 receptors are increased in patients with scleroderma.

Adult↗
PubMed1986

Murine basophil-mast differentiation: toward optimal conditions for selective growth and maturation of basophil-mast or allied cells.

Recent investigations revealed that basophil-mast cells were related to the hemopoietic system. Strikingly, murine bone marrow showed a singular paucity in cells with basophil-mast features; moreover in clonogenic assays (methylcellulose, agarose) bone marrow was found to be manifestly poor in basophil-mast progenitor cells. Our work brought to light several new facts concerning the culture and differentiation of this cell type: 1 degree pure and mixed mast clones can be derived in large numbers from bone marrow, provided progenitors are cultured in collagen matrix. Up to 1,382 hemopoietic clones were analysed in situ after staining: 30% contained mast cells (34 per 10(5) cells), thus the basophil-mast lineage was one of the most frequent. We concluded that other cloning media were noticeably nonoptimal for the growth and/or maturation of mast cells. We suggested that collagen and the molecular edifices derived from it, both found in variable amounts in the natural mast environments, should play essential roles in mast phenotype expression. 2 Degrees cholera toxin (CT) selectively eradicated nonmast progenies: mast progenitors and mast progenies were resistant. In this way, pure and rapidly expanding mast cell clones were obtained at a frequency never reported before. CT possibly acts both directly, as a stimulator of mast cell proliferation, or indirectly on marrow subpopulations which repress basophil-mast cell growth and maturation. In vitro culture conditions, specifically designed for basophil-mast lineage, should prove of interest in the search for an unifying hypothesis concerning the multiple forms of mast cells found in various tissues.

Animals↗
PubMed1986

Human basophil releasability. II. Changes in basophil releasability in patients with atopic dermatitis.

"Releasability" is the theory whereby biochemical events in basophils influence the capacity to release chemical mediators in response to activating stimuli. We have compared the releasability of basophils from 21 young patients with atopic dermatitis (AD) with that from 17 normal donors of matched ages. Basophils were challenged with several different stimuli: rabbit antihuman Fc epsilon (anti-IgE), N-formyl-methionyl-leucyl-phenylalanine (f-met-peptide), Ca++ ionophore A23187, and D2O. Basophils from patients with AD released significantly more histamine both "spontaneously" and in response to D2O than did controls. The basophils of patients with AD were significantly more responsive to anti-IgE and to A23187. There was no difference between the percent f-met-peptide-induced histamine release in patients with AD vs controls. No significant correlation between percent histamine release with optimal or suboptimal concentrations of the stimuli and serum IgE level was found. There was a significant correlation between the sensitivity of the cells to release with f-met-peptide and the response to A23187 both in control and in AD patients. Since basophils are thought to play some role at the site of inflammation in AD, their increased releasability might contribute to the symptoms of these patients.

Adolescent↗