Papers by H. F . Kauffman
Clinical & Experimental Allergy, 2000
Interleukin-3: its role in the physiopathology
of allergy and clinical use in oncology
The ''Regimen I'' and ''Regimen II'' annotations in the Kaplan-Meyer curves have been accidentall... more The ''Regimen I'' and ''Regimen II'' annotations in the Kaplan-Meyer curves have been accidentally reversed in both graphs 1A and 1B. The correct graphs appear below. A B
Interferon-c and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts
Interferon-g and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung... more Interferon-g and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts. F.M. Spoelstra, D.S. Postma, H. Hovenga, J.A. Noordhoek, H.F. Kauffman # ERS Journals Ltd 1999. ABSTRACT: The expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and more specifically vascular adhesion molecule-1 (VCAM-1) on lung fibroblasts may be important for migration of inflammatory cells through the submucosa to the airway lumen in the asthmatic inflammatory response. This study aimed to assess which cytokines are regulating ICAM-1 and VCAM-1 expression on human lung fibroblasts. For this purpose, confluent fibroblast cultures (derived from lung tissue from a nonasthmatic donor) were stimulated for 4 h with interleukin(IL)1b, tumour necrosis factor (TNF)a, interferon (IFN)c, IL-4, IL-5 or transforming growth factor (TGF)b. IL-1b (optimal concentration (OC) 1 U.mL) and TNFa (OC 100 U.mL) both increased ICAM-1 and VCAM-1 expression. IFNc (OC ...
The eosinophilic granulocyte an active participant in the late phase asthmatic reaction?
Bulletin européen de physiopathologie respiratoire, 1986
The role of the eosinophilic granulocyte in immediate hypersensitivity reactions is generally bel... more The role of the eosinophilic granulocyte in immediate hypersensitivity reactions is generally believed to be a beneficial one since this cell may phagocytose mast cell granules and inactivate certain mast cell mediators. However it has become clear that the eosinophilic granulocyte also has potent secretory capacities, and by this property may contribute in a detrimental way to the allergic process. In studying the late phase allergen induced bronchoconstriction by means of bronchoalveolar lavage (BAL) an evident infiltration of eosinophilic granulocytes in the bronchioli in the beginning of the late phase asthmatic reaction was noticed. Since also eosinophil cationic protein (ECP) has been reported to be elevated in the lavage fluid an active secretory role of the eosinophil in the late phase asthmatic reaction seemed likely. Although the release of ECP and other granular proteins may contribute to epithelial damage and inflammation and thereby to an increase in bronchial hyperreac...
Cyclosporine, FK506, Mycophenolate Mofetil, and Prednisolone Differentially Modulate Cytokine Gene Expression in Human Airway-Derived Epithelial Cells
Transplantation, 2000
The immunosuppressive effects of cyclosporine (CsA), tacrolimus (FK506), mycophenolate mofetil (M... more The immunosuppressive effects of cyclosporine (CsA), tacrolimus (FK506), mycophenolate mofetil (MMF), and prednisolone in cells from the immunological compartment are well documented. In contrast, limited information is available with respect to the effects of these immunosuppressive drugs on airway-epithelial cells, although these cells may contribute to the development of obliterative bronchiolitis (OB) through the production of interleukin (IL)-6 and IL-8. We studied the production of IL-6 and IL-8 proteins by airway-derived epithelial cell lines and primary epithelial cell cultures obtained from lung brushings. Transcriptional mechanisms were detected by transient transfections. We demonstrate that CsA dose dependently induces the production of the proinflammatory cytokines IL-6 and IL-8 in both cell lines and primary epithelial cells. FK506 and MMF were also able to upregulate IL-8, although the effect was less dramatic than observed for CsA. Low concentrations of prednisolone (0.01 and 0.001 microg/ml) enhanced IL-6 and IL-8 secretion, whereas concentrations > or =0.01 microg/ml significantly diminished IL-6 secretion. Furthermore, we showed that CsA and prednisolone mediate their effects at the transcriptional level. The data provide evidence that relevant concentrations of CsA and MMF in vivo may enhance the inflammatory processes in the lower airways of patients after lung transplantation.
Thorax, 1999
Background-Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has bee... more Background-Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO 2
Journal of Allergy and Clinical Immunology, 1989
A patient is described with an asymptomatic exacerbation of allergic bronchopulmonary aspergillos... more A patient is described with an asymptomatic exacerbation of allergic bronchopulmonary aspergillosis (ABPA), clinically characterized by pulmonary infiltrates, with absence of obstructive reactions and a short period of hemoptysis 2 weeks before hospitalization. Cell counts and antibody concentrations were measured in serum, and bronchoalveolar fluid (BAF) samples and values were compared with data from previous periods of symptomatic exacerbations. During the asymptomatic exacerbation, concentrations of antibody to Aspergillus fumigatus, total IgE, and precipitating antibodies were elevated in peripheral blood. No quantitative differences in speciJic antibody concentrations (IgE, IgG, &A, and IgM) against A. fumigatus were found between sera from symptomatic and asymptomatic periods of PBPA. In contrast to observations in the serum, protein concentrations in BAL fluid were normal during the asymptomatic period, whereas high concentrations were found during the symptomatic phases. Local antibody concentrations (in BAF) were characterized by high levels of IgA antibodies against A. fumigatus. During asymptomatic and symptomatic phases, eosinophils were elevated in peripheral blood, in sputum, in BAF, and highly elevated in tissue biopsy specimens. Activated eosinophils were found, as indicated by the presence of light-density cells in the circulation and monoclonal antieosinophil cationic protein binding to bronchoalveolar lavage eosinophils. In contrast to the symptomatic phase of ABPA in 1980, demonstrating aspect@ airway reactivity to several pharmacologically active substances, no such hyperreactivity was found during the asymptomatic phase of ABFA in 1986. It is proposed that the asymptomatic infiltrative phase of ABPA is an intermediate stage that can develop into a symptomatic phase after prolonged and intens$ed injiltration of eosinophils. Mediators from the inflammatory cells may be involved in the induction of bronchial hyperresponsiveness. After induction of this hyperreactive stage of the airways, additional liberation of mediators from either eosinophils andlor mast cells will lead to a symptomatic (obstructive) phase qf ABPA.
Journal of Allergy and Clinical Immunology, 1994
Background: Despite increasing evidence implicating fingal proteases in the virulence of pulmonat... more Background: Despite increasing evidence implicating fingal proteases in the virulence of pulmonaty fungal diseases, routine fungal culture media do not favor protease production. Hence, filtrates that serve as the source of antigen for serologic determinations are poor in proteases, and consequently, the immunologic sigr$cance of these enzymes is unknown. Methods: A clinical isolate of Aspergillus fumigatus was cultured on collagen medium, resulting in excretion of high levels of fungal proteases in the culture filtrate. This was compared with standard culture filtrates by diverse analytic techniques including immunoblotting with scra of patients with pulmonary aspergilloma (PA) and allergic bronchopulmonary aspergillosis (ABPA). Results: Protein profiles of collagen medium filtrate showed several (glyco)proteins not found in conventional culture filtrates, including a prominent 32 kd glycoprotein, which coisolated in gel filtration and ion-exchange chromatography with elastase activity, as well as 67 kd und 94 kd (glyco)proteins. Intense IgG binding was seen with the 32 kd glycoprotein when ABPA and PA sera were used. The 94 kd protein showed intense binding with PA sera but not with ABPA sera, whereas for the 67 kd glycoprotein the reverse tended to be the case. Conclusion: Fungal culture on collagen media results in the production of filtrates with high protease activity, containing unique (glyco)proteins of which at least one (32 kd) is close& associated with fungal elastase activi&. These constituents are immunologically relevant, eliciting IgG production in patients with PA and ABPA, suggesting production of these (glyco)proteins during disease in vivo. The use of collagen media filtrates may enhance our serodiagnostic capacity in patients with fungal pulmonary diseases.
American Journal of Respiratory and Critical Care Medicine, 1998
Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronc... more Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro , and if so, which activating factor is most important. CD11b and L-selectin expression of isolated peripheral blood eosinophils were measured by flow cytometry after coculture with normal lung fibroblasts or their conditioned medium. We found that eosinophil CD11b expression increased (154% and 210%, p Ͻ 0.05) and L-selectin expression decreased (59% and 35.5%, p Ͻ 0.05) on eosinophils compared with baseline (100%) after 4 and 24 h of coculture with interleukin-1-beta (IL-1 )-stimulated fibroblasts, respectively. Conditioned medium of stimulated fibroblasts also increased CD11b expression, but to a smaller extent (p Ͻ 0.05). L-selectin expression of eosinophils in cocultures was not different from that of eosinophils in conditioned medium. Only anti-granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) reduced the activation of eosinophils in conditioned medium to almost basal levels (p Ͻ 0.05). An increase in CD11b expression is mediated by cytokines as well as direct cell contact, whereas a decrease in L-selectin expression is only mediated by cytokines. GM-CSF released by fibroblasts is an important factor in the modulation of both CD11b and L-selectin expression. These results show that lung fibroblasts can activate eosinophils by both adhesive interactions and by soluble factors. Spoelstra FM, Hovenga H, Noordhoek JA, Postma DS, Kauffman HF. Changes in CD11b and L-selectin expression on eosinophils are mediated by human lung fibroblasts in vitro .
American Journal of Respiratory and Critical Care Medicine, 1996
The factors that lead to increased production of specific IgG subclasses are still largely unknow... more The factors that lead to increased production of specific IgG subclasses are still largely unknown. Recent studies suggest that increased IgG4 responses may be related to prolonged antigen exposure. We present data showing that increased IgG4 responses are found under conditions of chronic exposure to Aspergillus fumigatus (At) antigen. IgG(total), IgG subclass, and IgE responses were studied using ELISA, CAP-FEIA, and immunoblotting techniques in patients with pulmonary aspergilloma (PA), which is a model for chronic antigen exposure, and allergic bronchopulmonary aspergillosis (ABPA), characterized by transient antigen exposure. Af-lgG1 was increased in patients with PAcompared with those with ABPA. Patients with PA and IgE responses to Af and/or other inhalant allergens showed significantly higher Af-lgG4 responses than did patients with PAand negative IgE responses or patients with ABPA. Surveillance studies over time in individual patients showed concordance in Af-lgG1 and Af-lgG4 responses. Both Af-lgG1 and Af-lgG4 levels followed the course of disease progression and treatment. Immunoblotting revealed correlations between Af-lgG1 and Af-lgG4 binding to most, but not all, antigenic Af components. This study documents for the first time increased IgG4 levels under conditions of chronic exposure to fungal antigen in PA. Furthermore, a significantly higher IgG4 response was found in those patients with PA who produced IgE. The transient exposure to Af antigen during exacerbation of ABPA gives rise to transient elevations in IgG4 levels. Tomee JFC, Dubois AEJ, Koeter GH, Beaumont F, van der Wert TS, Kauffman HF. Specific IgG4 responses during chronic and transient antigen exposure in aspergillosis.
American Journal of Respiratory and Critical Care Medicine, 2000
In a prospective cohort study, we assessed whether changes in total cell counts and differentiati... more In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n ϭ 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV у 80% of baseline (n ϭ 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p Ͼ 0.05). In the bronchial fraction, median total cell counts (0.06 ϫ 10 3 /ml versus 0.04 ϫ 10 3 /ml), lymphocyte (9 ϫ 10 3 /ml versus 2 ϫ 10 3 /ml), and eosinophilic granulocyte counts (1 ϫ 10 3 /ml versus 0) were significantly higher in the OB group than in the GO group (p Ͻ 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 ϫ 10 3 /ml versus 4 ϫ 10 3 /ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.
Changes in the beta-adrenergic system in bronchial asthma induced by terbutaline
Agents and actions. Supplements, 1983
Optimization, standardization and control of food allergens
Monographs in allergy, 1996
Agents and Actions, 1985
In order to investigate the role of histamine in the late asthmatic reaction (LAR) following hous... more In order to investigate the role of histamine in the late asthmatic reaction (LAR) following house-dust mite (HDM) inhalation, we studied, with hourly intervals, urinary NT-methylhistamine (an important metabolite of histamine) in 14 allergic asthmatic patients before and after broncho provocation with HDM. Four patients showed an early asthmatic reaction (EAR), while 10 patients developed a LAR as well. In the hour following the EAR a significant increase in urinary N'-methylhlstamine was observed as compared to the control day (0.01 < p < 0.05). During the LAR no increase ofthls metabollte was detected in the urine of the patients. Additionally, histamine was measured in broncho alveolar lavage fluid (BAF) obtained from 6 patients during the HDM-provoked LAR and compared to histamine levels in BAF from patients without a LAR, following broncho provocation. In the LAR group higher histamine levels were found than in the other patient and control groups. For the whole patient group no correlation was found between the degree of bronchial obstruction during the LAR and the BAF histamine values. No difference was found in NT-methylhistamine in BAF between patients with LAR and controls. Thus histamine metabollte studies in the urine failed to provide evidence of involvement of histamine in the LAR, while further data are needed to interpret the results of local sampling in the lung.
Journal of Allergy and Clinical Immunology, 1989
Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions
The American review of respiratory disease, 1985
In order to obtain information about the nature of the local inflammatory process during late ast... more In order to obtain information about the nature of the local inflammatory process during late asthmatic reactions after house dust mite inhalation, bronchoalveolar lavage (BAL) was performed in 19 asthmatic patients and in 5 control subjects. In 16 of the patients and in all of the control subjects, BAL was performed 6 to 7 h after allergen inhalation. Six of the patients showed early and late asthmatic reactions (LAR), 5 showed early reactions, and 5 showed no reactions. Bronchoalveolar lavage was also performed shortly after the early reaction in 5 patients with documented combined early and late reactions. In the BAL fluid of the patients with LAR, a significant eosinophilia (0.01 less than p less than 0.05) was found compared with that in all other patient groups and with that in the control subjects. This bronchoalveolar eosinophilia was accompanied by elevated eosinophil cationic protein/albumin ratio in the BAL fluid (0.01 less than p less than 0.05). These observations sugge...
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 1998
To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-relate... more To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-related emphysema, we performed immunohistochemical studies in lung tissue from control subjects and patients with mild and severe emphysema. We studied the presence of inducible and endothelial NO synthases (iNOS and eNOS, respectively) and determined nicotinamide diphosphate (NADPH) diaphorase activity. Patients with severe emphysema showed lower percentages of iNOS- and eNOS-positive alveolar macrophages in situ than did patients with mild emphysema. In patients with both iNOS and eNOS immunoreactivity in macrophages, the majority of the macrophages expressed either iNOS or eNOS, whereas only a minority of the macrophages showed iNOS and eNOS immunoreactivity simultaneously. Immunoreactivity for eNOS in endothelial and/or bronchiolar epithelial cells and NADPH diaphorase activity in macrophages and in endothelial, epithelial, and smooth muscle cells were similar in the three studied groups....
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1996
We investigated the role of IL-7 on the expression of IFN-gamma and IL-4 in human T lymphocytes. ... more We investigated the role of IL-7 on the expression of IFN-gamma and IL-4 in human T lymphocytes. IL-7 alone did not induce IFN-gamma or IL-4 mRNA. However, IL-7 dose-dependently up-regulates the anti-CD3- or anti-CD3/anti-CD28-induced IFN-gamma and IL-4 mRNA expression. Used at an optimal concentration, IL-7 (5 ng/ml) increased the accumulation of IFN-gamma (eightfold) and IL-4 (2.5-fold) mRNAs, which could not be blocked by anti-IL-12 treatment. The enhanced IFN-gamma mRNA accumulation was observed within 3 to 6 h, without altering the pattern of the kinetics. However, longer exposure (> 12 h) did not result in different IFN-gamma expression for anti-CD3/anti-CD28 vs anti-CD3/anti-CD28 plus IL-7-stimulated T lymphocytes. mRNA stability studies revealed that IL-7 stabilizes both IFN-gamma and IL-4 mRNA transcripts: 40 and 60 min in anti-CD3/anti-CD28-stimulated T cells vs 120 and 90 min in T cells costimulated with anti-CD3/anti-CD28 plus IL-7. Nuclear run-on assays revealed that...
The role of the adrenergic system in allergy and bronchial hyperreactivity
European journal of respiratory diseases. Supplement, 1982
The adrenergic system may have an influence on the severity and activity of bronchial asthma. It ... more The adrenergic system may have an influence on the severity and activity of bronchial asthma. It has been suggested that there might be a relationship between the allergic process and the adrenergic system. Therefore this system was studied before and after an allergen challenge. Two parameters were measured: in vivo: propranolol threshold measurement to assess adrenergic involvement; in vitro: the beta-adrenergic response of peripheral lymphocytes as parameter for beta-receptor function. Seven allergic asthmatics who were not treated with beta-stimulants or corticosteroids and seven normals inhaled house dust mite extract. On the days before and after the challenge, propranolol threshold measurements were performed. Six patients had a dual reaction after a house dust mite inhalation; one patient had an early response. The propranolol threshold changed from 1.32% (SEM 0.16) on the day before challenge to 0.86% (SEM 0.19) on the day after (0.02 less than P less than 0.025). In the sa...
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Papers by H. F . Kauffman