Allergic reactions to foods are driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE- ... more Allergic reactions to foods are driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE- expressing cells can be generated through a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is important in generating high affinity IgE, augmenting anaphylactic reactions, and in holding the memory of IgE responses. Here, we observed surprising redundancy of sequential switching through IgG1 for the functional affinity of the IgE repertoire against multiple food allergens as well as for the ability of IgE to elicit anaphylaxis. We further found that sequential switching via IgG1 was irrelevant for allergic memory. These results indicate that allergen-specific IgG1 B cells are redundant in sensitization, anaphylaxis, and food allergy persistence, thereby implicating other switching pathways as important considerations in the developmen...
Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis... more Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. We report a population of type 2 polarized MBCs defined as CD23hi, IL-4Rαhi, CD32lowat the transcriptional and surface protein levels. These “MBC2s” are enriched in IgG1 and IgG4-expressing cells, while constitutively expressing germline transcripts for IgE. Allergen-specific B cells from patients with allergic rhinitis and food allergy were enriched in MBC2s. MBC2s generated allergen specific-IgE during sublingual immunotherapy, thereby identifying these cells as the primary reservoir of IgE. The identification of MBC2s provides insights into the maintenance of IgE memory, which is detrimental in allergic diseases, but which could be beneficial in protection against venoms and helminths.One-Sentence SummaryIdentification of a novel memory B cell subs...
Intestinal Th2 immunity in food allergy results in the production of IgG1 and IgE, and upon antig... more Intestinal Th2 immunity in food allergy results in the production of IgG1 and IgE, and upon antigen challenge, anaphylaxis and eosinophilic inflammation. Although allergic sensitization critically requires IL-4 to develop, the source and control of IL-4 during the initiation of Th2 immunity remains unclear. Non-intestinal and non-food allergy systems have suggested a role for innate lymphocytes such as NKT or γδ T cells as a rapid source of IL-4 required to induce Th2 polarization. In contrast, we show here that NKT-deficient IL-15 KO, β2m KO and anti-NK1.1 treated mice have completely intact Th2 food allergic responses comparable to NKT-sufficient mice, including antigen-specific IgG1 and IgE, anaphylaxis, eosinophilic inflammation and cytokine production. Likewise, γδ T cell-deficient TCRδ KO mice mount comparable Th2 immune responses to oral antigen as their WT counterparts. By restricting IL-4 expression to only CD4+ Th cells, we find that IL-4 from CD4+ Th cells themselves indu...
Background: Mast cells (MCs) play a sentinel role in innate immunity. However, little is known re... more Background: Mast cells (MCs) play a sentinel role in innate immunity. However, little is known regarding the role of MCs in viral infections in human in vivo conditions. This study characterizes MCs in the lungs from infants who have died in acute respiratory viral infections. Methods: Lung tissue from infants who died in respiratory syncytial virus (RSV, n=5), adenovirus (n=11) and influenza (n=6) infections was processed for immunohistochemical identification of MCT and MCTC and related mediators. Ten infants who died of non-respiratory causes were used as controls. We also examined MC alterations in a mouse model of exposure to the common aeroallergen house dust mite (HDM) during the course of an influenza infection. Results: An increase in both MCT and MCTC numbers was observed in the alveolar parenchyma in infants infected with RSV (p=0.02), adenovirus (p=0.001) and influenza (p=0.02) compared to the controls. No differences were found in small airways or pulmonary vessels. High MC expression of pattern recognition receptors and pro-inflammatory cytokines were present in the infected lungs. In the mouse model, alveolar MC numbers were increased 3 weeks after infection (p=0.006), HDM (p=0.01) and when combining HDM and influenza (p=0.002) compared to saline treated animals. Increased MC numbers were still significant 6 week after infection. Conclusions: These data demonstrate that a viral infection in peripheral airways evokes a rapid expansion of MC populations both in mice and humans. These findings support a role for MCs in the immune response to respiratory viral infections. Our animal data also indicates an important link between allergic sensitization and viral infection.
Background: Asthma usually develops during childhood and is associated with increased numbers of ... more Background: Asthma usually develops during childhood and is associated with increased numbers of lung MCs (MCs). Whether viral infections in young children can cause increased MC numbers and contribute to asthma development is unknown. We sought to investigate if lower respiratory tract infections (LRTIs) cause alterations in lung MC populations in children. Methods: Lung tissue from 21 young children who died following LRTIs was processed for immunohistochemical identification of MCs and related mediators. Ten children who died from non-respiratory causes were used as controls. MC changes in relation to sensitization were further examined in infant mice exposed to house dust mite (HDM) during the course of influenza A infection. Results: An increased number of MCs were observed in the alveolar parenchyma of young children infected with LRTIs compared to controls. This was associated with a higher frequency of CD34 + tryptase + MC progenitors and an increased expression of vascular cell adhesion molecule (VCAM)-1. Similar to children with LRTIs, infant mice infected with influenza A had an increased number of alveolar MCs. MCs numbers continued to increase and remained significantly higher at 6 weeks post infection and allergy challenge. Conclusions: The results from our study demonstrate that a viral infection affecting the peripheral lung evokes a rapid accumulation of MCs in the alveolar parenchyma in both infant humans and mice. Since MCs are very long-lived and are likely to remain in the tissue after the infection has been cleared, a notion supported by the animal data, the increased MC numbers might also affect susceptibility towards allergens and asthma development later in life.
/ Thematic Poster Session / Wednesday, May 19/8:15 AM-4:00 PM / Area D31 ANIMAL MODELS OF AIRWAY ... more / Thematic Poster Session / Wednesday, May 19/8:15 AM-4:00 PM / Area D31 ANIMAL MODELS OF AIRWAY INFLAMMATION ... E, Hall G (First Level), Morial Convention Center ... Influenza-A Infection Alters The Immune Responsiveness To House Dust Mite In ...
BackgroundFood allergy, in particular peanut allergy, is a growing concern in Western countries. ... more BackgroundFood allergy, in particular peanut allergy, is a growing concern in Western countries. The prevalence of allergy to peanut, which currently stands at 1.4%, nearly tripled between 1997 and 2008. Allergic sensitization is a particularly difficult process to study as it is clinically silent.We sought to identify key pathways and mediators critically involved in the induction of allergic sensitization to peanut.MethodsComprehensive metabolomics analysis with liquid chromatography–mass spectrometry was used to detect metabolite changes in mice (C57BL/6) undergoing sensitization. Loss‐of‐function and gain‐of‐function studies were performed in mice subjected to two models of peanut sensitization and anaphylaxis that involved either oral or epicutaneous sensitization. Flow cytometric analyses on dendritic cells (DCs) in vitro and in vivo were used to investigate the mechanisms of immune activation.ResultsElevated levels of uric acid (UA) were detected in mice undergoing sensitizat...
SUMMARYOriginally defined by their patterns of cytokine production, Th1 and Th2 cells have been d... more SUMMARYOriginally defined by their patterns of cytokine production, Th1 and Th2 cells have been described more recently to express other genes differentially as well, at least in vitro. In this study we compared the expression of Th1- and Th2-associated genes directly during in vivo sensitization to ovalbumin (OVA) in Th1- and Th2-polarized models of airways inflammation. Th1-polarized airway inflammation was achieved by the intranasal instillation of adenoviral vectors (Ad) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-12, followed by daily aerosolizations of OVA; instillation of Ad/GM-CSF alone with OVA aerosolization led to Th2-polarized responses. Lymph nodes were obtained at various time-points, RNA extracted, and analysed by real-time quantitative polymerase chain reaction (PCR). Consistent with reports from in vitro and human studies, mice undergoing Th1-polarized inflammation showed preferential expression of the transcription factor...
... JACK GAULDIE, MANEL JORDANA, GERARD COX, TAKAYUKI OHTOSHI, JERRY DOLOVICH, and ... Most of th... more ... JACK GAULDIE, MANEL JORDANA, GERARD COX, TAKAYUKI OHTOSHI, JERRY DOLOVICH, and ... Most of the cytokines have been discovered and de-scribed initially by their apparent function, and many are now known to have primary functions in vivo that are not ...
The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the conce... more The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Epithelial cells lining mucosal tissues traditionally provide physical defence against external m... more Epithelial cells lining mucosal tissues traditionally provide physical defence against external microbes, while allowing selective absorption. A more sophisticated contribution to defence was recognized with the description of the secretory immune system, where transport across epithelial cells was dependent upon surface receptors for dimeric IgA, and the observation that the local immune response could in turn regulate uptake of macromolecules.’ A more complex relationship between epithelial cells and both innate and adaptive immunity has been recognized with the observation that epithelial cells can present antigen from the environment to lymphoid cells. More recently, it has become evident that epithelial cells can produce a number of cytokine messenger molecules capable of significantly influencing inflammation. These newly recognized functions of mucosal epithelial cells are the focus of this paper.
American Journal of Respiratory Cell and Molecular Biology, 1991
We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep... more We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergic reactions to foods are driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE- ... more Allergic reactions to foods are driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE- expressing cells can be generated through a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is important in generating high affinity IgE, augmenting anaphylactic reactions, and in holding the memory of IgE responses. Here, we observed surprising redundancy of sequential switching through IgG1 for the functional affinity of the IgE repertoire against multiple food allergens as well as for the ability of IgE to elicit anaphylaxis. We further found that sequential switching via IgG1 was irrelevant for allergic memory. These results indicate that allergen-specific IgG1 B cells are redundant in sensitization, anaphylaxis, and food allergy persistence, thereby implicating other switching pathways as important considerations in the developmen...
Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis... more Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. We report a population of type 2 polarized MBCs defined as CD23hi, IL-4Rαhi, CD32lowat the transcriptional and surface protein levels. These “MBC2s” are enriched in IgG1 and IgG4-expressing cells, while constitutively expressing germline transcripts for IgE. Allergen-specific B cells from patients with allergic rhinitis and food allergy were enriched in MBC2s. MBC2s generated allergen specific-IgE during sublingual immunotherapy, thereby identifying these cells as the primary reservoir of IgE. The identification of MBC2s provides insights into the maintenance of IgE memory, which is detrimental in allergic diseases, but which could be beneficial in protection against venoms and helminths.One-Sentence SummaryIdentification of a novel memory B cell subs...
Intestinal Th2 immunity in food allergy results in the production of IgG1 and IgE, and upon antig... more Intestinal Th2 immunity in food allergy results in the production of IgG1 and IgE, and upon antigen challenge, anaphylaxis and eosinophilic inflammation. Although allergic sensitization critically requires IL-4 to develop, the source and control of IL-4 during the initiation of Th2 immunity remains unclear. Non-intestinal and non-food allergy systems have suggested a role for innate lymphocytes such as NKT or γδ T cells as a rapid source of IL-4 required to induce Th2 polarization. In contrast, we show here that NKT-deficient IL-15 KO, β2m KO and anti-NK1.1 treated mice have completely intact Th2 food allergic responses comparable to NKT-sufficient mice, including antigen-specific IgG1 and IgE, anaphylaxis, eosinophilic inflammation and cytokine production. Likewise, γδ T cell-deficient TCRδ KO mice mount comparable Th2 immune responses to oral antigen as their WT counterparts. By restricting IL-4 expression to only CD4+ Th cells, we find that IL-4 from CD4+ Th cells themselves indu...
Background: Mast cells (MCs) play a sentinel role in innate immunity. However, little is known re... more Background: Mast cells (MCs) play a sentinel role in innate immunity. However, little is known regarding the role of MCs in viral infections in human in vivo conditions. This study characterizes MCs in the lungs from infants who have died in acute respiratory viral infections. Methods: Lung tissue from infants who died in respiratory syncytial virus (RSV, n=5), adenovirus (n=11) and influenza (n=6) infections was processed for immunohistochemical identification of MCT and MCTC and related mediators. Ten infants who died of non-respiratory causes were used as controls. We also examined MC alterations in a mouse model of exposure to the common aeroallergen house dust mite (HDM) during the course of an influenza infection. Results: An increase in both MCT and MCTC numbers was observed in the alveolar parenchyma in infants infected with RSV (p=0.02), adenovirus (p=0.001) and influenza (p=0.02) compared to the controls. No differences were found in small airways or pulmonary vessels. High MC expression of pattern recognition receptors and pro-inflammatory cytokines were present in the infected lungs. In the mouse model, alveolar MC numbers were increased 3 weeks after infection (p=0.006), HDM (p=0.01) and when combining HDM and influenza (p=0.002) compared to saline treated animals. Increased MC numbers were still significant 6 week after infection. Conclusions: These data demonstrate that a viral infection in peripheral airways evokes a rapid expansion of MC populations both in mice and humans. These findings support a role for MCs in the immune response to respiratory viral infections. Our animal data also indicates an important link between allergic sensitization and viral infection.
Background: Asthma usually develops during childhood and is associated with increased numbers of ... more Background: Asthma usually develops during childhood and is associated with increased numbers of lung MCs (MCs). Whether viral infections in young children can cause increased MC numbers and contribute to asthma development is unknown. We sought to investigate if lower respiratory tract infections (LRTIs) cause alterations in lung MC populations in children. Methods: Lung tissue from 21 young children who died following LRTIs was processed for immunohistochemical identification of MCs and related mediators. Ten children who died from non-respiratory causes were used as controls. MC changes in relation to sensitization were further examined in infant mice exposed to house dust mite (HDM) during the course of influenza A infection. Results: An increased number of MCs were observed in the alveolar parenchyma of young children infected with LRTIs compared to controls. This was associated with a higher frequency of CD34 + tryptase + MC progenitors and an increased expression of vascular cell adhesion molecule (VCAM)-1. Similar to children with LRTIs, infant mice infected with influenza A had an increased number of alveolar MCs. MCs numbers continued to increase and remained significantly higher at 6 weeks post infection and allergy challenge. Conclusions: The results from our study demonstrate that a viral infection affecting the peripheral lung evokes a rapid accumulation of MCs in the alveolar parenchyma in both infant humans and mice. Since MCs are very long-lived and are likely to remain in the tissue after the infection has been cleared, a notion supported by the animal data, the increased MC numbers might also affect susceptibility towards allergens and asthma development later in life.
/ Thematic Poster Session / Wednesday, May 19/8:15 AM-4:00 PM / Area D31 ANIMAL MODELS OF AIRWAY ... more / Thematic Poster Session / Wednesday, May 19/8:15 AM-4:00 PM / Area D31 ANIMAL MODELS OF AIRWAY INFLAMMATION ... E, Hall G (First Level), Morial Convention Center ... Influenza-A Infection Alters The Immune Responsiveness To House Dust Mite In ...
BackgroundFood allergy, in particular peanut allergy, is a growing concern in Western countries. ... more BackgroundFood allergy, in particular peanut allergy, is a growing concern in Western countries. The prevalence of allergy to peanut, which currently stands at 1.4%, nearly tripled between 1997 and 2008. Allergic sensitization is a particularly difficult process to study as it is clinically silent.We sought to identify key pathways and mediators critically involved in the induction of allergic sensitization to peanut.MethodsComprehensive metabolomics analysis with liquid chromatography–mass spectrometry was used to detect metabolite changes in mice (C57BL/6) undergoing sensitization. Loss‐of‐function and gain‐of‐function studies were performed in mice subjected to two models of peanut sensitization and anaphylaxis that involved either oral or epicutaneous sensitization. Flow cytometric analyses on dendritic cells (DCs) in vitro and in vivo were used to investigate the mechanisms of immune activation.ResultsElevated levels of uric acid (UA) were detected in mice undergoing sensitizat...
SUMMARYOriginally defined by their patterns of cytokine production, Th1 and Th2 cells have been d... more SUMMARYOriginally defined by their patterns of cytokine production, Th1 and Th2 cells have been described more recently to express other genes differentially as well, at least in vitro. In this study we compared the expression of Th1- and Th2-associated genes directly during in vivo sensitization to ovalbumin (OVA) in Th1- and Th2-polarized models of airways inflammation. Th1-polarized airway inflammation was achieved by the intranasal instillation of adenoviral vectors (Ad) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-12, followed by daily aerosolizations of OVA; instillation of Ad/GM-CSF alone with OVA aerosolization led to Th2-polarized responses. Lymph nodes were obtained at various time-points, RNA extracted, and analysed by real-time quantitative polymerase chain reaction (PCR). Consistent with reports from in vitro and human studies, mice undergoing Th1-polarized inflammation showed preferential expression of the transcription factor...
... JACK GAULDIE, MANEL JORDANA, GERARD COX, TAKAYUKI OHTOSHI, JERRY DOLOVICH, and ... Most of th... more ... JACK GAULDIE, MANEL JORDANA, GERARD COX, TAKAYUKI OHTOSHI, JERRY DOLOVICH, and ... Most of the cytokines have been discovered and de-scribed initially by their apparent function, and many are now known to have primary functions in vivo that are not ...
The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the conce... more The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Epithelial cells lining mucosal tissues traditionally provide physical defence against external m... more Epithelial cells lining mucosal tissues traditionally provide physical defence against external microbes, while allowing selective absorption. A more sophisticated contribution to defence was recognized with the description of the secretory immune system, where transport across epithelial cells was dependent upon surface receptors for dimeric IgA, and the observation that the local immune response could in turn regulate uptake of macromolecules.’ A more complex relationship between epithelial cells and both innate and adaptive immunity has been recognized with the observation that epithelial cells can present antigen from the environment to lymphoid cells. More recently, it has become evident that epithelial cells can produce a number of cytokine messenger molecules capable of significantly influencing inflammation. These newly recognized functions of mucosal epithelial cells are the focus of this paper.
American Journal of Respiratory Cell and Molecular Biology, 1991
We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep... more We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM.(ABSTRACT TRUNCATED AT 250 WORDS)
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