Biomedical subjects

A B Tonnel

Publications and source records attributed to A B Tonnel.

At least 19 recordsLinked to original sources

PubMed1992

[Physiopathology of asthma].

Asthma is a multifactorial disease where genetic predisposition, environmental factors (allergens and pollutants) and endogenous factors intervene to varying degrees. Among the disturbances involved in the physiopathology of asthma dysfunction of the autonomic nervous system and development of bronchial inflammation are now known to play the major roles. From the adrenergic system, the role of which is now controverted, the attention of pharmacologists has shifted to the cholinergic central nervous system responsible for bronchial tone and the non adrenergic non cholinergic (NANC) nervous system. The more recently known NANC system is complex and mediated by neuropeptides, and it can alternately induce bronchodilatation and bronchoconstriction, as well as vasoconstriction and vasodilatation. The inhibitory NANC system acts through the bronchodilator VIP. The excitatory NANC system is mediated by tachykinins as which are potent bronchoconstrictors. Interaction of this system with the inflammatory cells induces a "neurogenic inflammation". Local inflammatory reaction is an almost constant element of asthma, irrespective of the cause of the disease. Although mast cells are the initial cells of the inflammatory reaction, there are important and complex cellular interactions with eosinophils, macrophages, lymphocytes and epithelial cells. Owing to their direct cytotoxic actions on the bronchial epithelium, eosinophils play a key-role in the inflammatory reaction. Cytokines secreted by alveolar macrophages, lymphocytes and mast cells amplify and maintain the inflammatory process.

Asthma↗

PubMed1992

Human endothelial cells transfected by SV40 T antigens: characterization and potential use as a source of normal endothelial factors.

A putative role for the vascular endothelium as target for autoantibodies has been suggested in several autoimmune disorders and connective-tissue diseases. However, there are some difficulties linked to the use of cultured endothelial cells (EC) that limit considerably the extensive studies on the nature of endothelial target antigens involved. To overcome this problem, human EC, derived from umbilical veins, were transfected with recombinant plasmid pSV1 which contained the early genes of simian virus SV40. These transfected cells, called EC-pSV1, are able to grow without EC growth supplement and demonstrate a population doubling time of about 50 h. Among the EC properties, EC-pSV1 retain intracellular content of angiotensin-converting enzyme activity, exhibit constitutive production of interleukin 6 and of a growth-promoting activity on early passage EV, express intercellular adhesion molecule 1 (ICAM-1) and its up-regulation by tumor necrosis factor alpha, but have lost the expression of factor VIII-related antigen. Moreover, EC-pSV1 express a 55-kDa antigen found on EC and human platelets, and presumably acting as an antibody target in some cases of non-allergic asthma. However, at the 50-55th generation, morphological changes and altered growth behavior were visible. This work demonstrates that transfection of EC with SV40 T antigens may be of interest, particularly in areas of research including the study of EC targets involved in different human diseases.

Antigens, Polyomavirus Transforming↗

PubMed1992

Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy.

Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma.

Adrenal Cortex Hormones↗

PubMed1992

Increased intestinal permeability in active pulmonary sarcoidosis.

Altered permeability of the gut is a well-described feature in Crohn's disease. Because of pathologic similarities between Crohn's disease and sarcoidosis, we initiated this study to evaluate the permeability of the gut mucosal lining in patients with pulmonary sarcoidosis. A group of 18 patients with biopsy-proven pulmonary sarcoidosis (active n = 8, inactive n = 10) were included in the study. Control groups included 22 patients with Crohn's disease (active n = 12, inactive n = 10), nine untreated patients with recent pulmonary tuberculosis, six patients with coal worker's pneumoconiosis (CWP), eight patients with idiopathic pulmonary fibrosis (IPF), and 16 healthy subjects. All were nonsmokers. The 24-h urinary excretion of 100 microCi 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) was used to test the intestinal permeability (IP). As previously demonstrated, patients with active Crohn's disease demonstrated a dramatic increase in IP (7.7 +/- 1.4%) that was clearly reduced in inactive CD (2.34 +/- 0.54%). Patients with active pulmonary sarcoidosis exhibited a marked increased IP to 51Cr-EDTA (4 +/- 0.54%), which was not found in patients with inactive sarcoidosis (1.6 +/- 0.17%). IP was normal in patients with pulmonary tuberculosis (1.03 +/- 0.25%), CWP (2.1 +/- 0.54%), and IPF (1.9 +/- 0.33%) and did not differ from the control group (1.76 +/- 0.23%). In addition, in 6 patients with active pulmonary sarcoidosis, the concentrations of albumin and hyaluronan were measured in jejunal perfusion fluid and compared with those obtained from 10 patients with active Crohn's disease and 16 control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

PubMed1992

Long-term prognosis of near-fatal asthma. A 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma.

The objective of the present study was to investigate the long-term prognosis of near-fatal asthma. A retrospective cohort study design was used. Cases were defined as any asthmatic individual requiring mechanical ventilation for the first time for an asthma exacerbation between January 1, 1983 and December 31, 1988. The consecutive sample of patients was drawn from four study sites, specifically four intensive care units (ICU), based in a large urban area (1 million inhabitants). These four ICU total approximately 5,000 admissions per year and are the referral centers for more than 95% of patients requiring respiratory intensive care in the area. Data collection was obtained by questionnaires addressed to the patients and to their attending physicians and was completed by telephone calls if necessary. A total of 147 patients entered the study. The long-term outcome could be evaluated in all but two patients. The follow-up period ranged from 1 to 75 months. In-hospital mortality was 16.5%. Among the 121 patients discharged from the ICU, 18 subsequently died, 17 of whom died from a new attack of asthma. Post-hospitalization mortality was 10.1% (95% CI, 5.9 to 16.8%) after 1 yr, 14.4% (CI, 9 to 22.3%) after 3 yr, and 22.6% (CI, 12.7 to 36.8%) after 6 yr. Nearly two-thirds (61.5%) of these secondary deaths occurred within the year following discharge from the ICU. Smoking was associated with a higher in-hospital mortality, as well as with a higher posthospitalization mortality. Age was also independently associated with a higher posthospitalization mortality. It is noteworthy that the secondary deaths were mostly observed in patients over 40 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1992

Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation.

We have previously demonstrated the production of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 than did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects).(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

PubMed1992

Bronchoalveolar lavage in alcoholic liver cirrhosis. T-lymphocyte subsets and immunoglobulin concentrations.

The purpose of this study was to determine the phenotype profiles of immune effector cells and the concentrations of immunoglobulins in the lower respiratory tract of non-smoking patients with alcoholic liver cirrhosis (ALC). Nine nonsmoking patients with liver biopsy-proved ALC (grade B or C cirrhosis in Child's classification), free of clinical pulmonary symptoms, and with normal chest roentgenogram were included in the study. The control group included 12 healthy nonsmokers. Each patient had fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The number of T cells and of lymphocyte subpopulations was determined by immunofluorescence studies using monoclonal antibodies that were specific for CD3, CD4, and CD8 markers. Patients with ALC exhibited a dramatically increased percentage of CD8+ cells in BAL that induced a low CD4/CD8 ratio (0.96 +/- 0.15 vs 1.8 +/- 0.12 in healthy controls). Further characterization of lymphocyte subsets' dual immunofluorescence analysis demonstrated that most of the CD8+ alveolar lymphocytes had a phenotype of cytotoxic cells (CD8+ CD11b-; 48 percent +/- 13 in ALC vs 10 percent +/- 5 in controls). ALC was associated with an appreciable alveolar-capillary "leak" as demonstrated by a significant increase in BAL fluid albumin. In addition, the concentrations of immunoglobulins in BAL fluid were significantly greater in ALC than in controls. However, the relative (to albumin) coefficient of excretion of IgG, A, and M in and alpha 2-macroglobulin BAL fluid was not significantly different between controls and ALC. Our results indicate that increased proportions of CB8+ and especially of CD8+ CD11b- cells are a common feature in the lower respiratory tract of nonsmoking patients with ALC. These changes may be of potential functional importance in the regulation of the local pulmonary immune response in ALC.

Adult↗

PubMed1992

[The multifocal form of bronchocentric granulomatosis].

Bronchocentric granulomatosis is a rare entity and has only recently been characterised. We report a case of a forty-three year old man presenting with multifocal bronchocentric granulomatosis which was revealed following some oto-rhino-laryngological and bronchopulmonary symptoms. The open lung biopsy confirmed the diagnosis. Treatment was by bolus doses of corticosteroids (30 mg/kg) and of methotrexate in low dosage (7.5 mg/week, then 15 mg/week) which checked the initially unfavourable outcome.

Adrenal Cortex Hormones↗

PubMed1992

[Adenocarcinomatous pleural lesion associated with hypoglycemia].

We report the case of a patient suffering from a glandular pleural lesion. The evolution of the disease was punctuated by periods of hypoglycaemia, which caused a coma. There was no clinically evident explanation for these hypoglycaemic episodes. Investigations revealed adrenal failure, but this adrenal failure was unrelated to the neoplastic process in the patient. This case is a reminder that the cause of hypoglycaemia associated with tumours can really have a paraneoplastic origin and justifies an in depth study to achieve an aetiological diagnosis.

Adenocarcinoma↗

PubMed1991

[Significance of an increase of total IgE].

Under normal condition, serum IgE concentrations are low and controlled by complex regulating mechanisms. Increased IgE synthesis may be associated with a response of IgE antibodies to allergens or parasites. It may also betray a wider disorder in the regulation of IgE production, resulting in a rise of total IgEs of unknown specificity. Broadly speaking, high IgE levels are observed in two main circumstances: allergic ans parasitic diseases. In allergic diseases the diagnostic value of high IhE concentrations is modest, since a search for specific IgEs by cutaneous tests ot laboratory techniques (RAST) is more rewarding than total IgE determination. However, total IgE assays are useful in the detection of atopy in neonates at risk and the identification and therapeutic follow-up of allergic pulmonary aspergillosis. High IgE levels are frequently associated with parasitic diseases, especially helminthiasis. They also reflect a disorder of IgE homeostasis in some types of immunodeficiency, including the classical IgE hyperproduction syndrome. Except for this syndrome, high IgE concentrations merely constitute a secondary diagnostic factor in a wide pathology, but they often bear witness to a subjacent dysregulation of T-cell function.

Adult↗

PubMed1991

Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation.

The release of eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) was evaluated after incubation of eosinophils (EOSs) from allergic subjects with the specific allergen or with anti-IgE monoclonal antibodies (MAbs). High levels of EPO could be released after addition of the specific allergen (and not unrelated ones) or anti-IgE MAb. Moreover, EPO release with the two stimuli was significantly correlated both in allergic and in nonallergic patients. In the same supernatants, another granule protein, ECP, could not be detected, suggesting a lack of correlation between EPO and ECP release after IgE-dependent stimulation. However, when EOSs with surface-IgA antibodies were incubated with anti-IgA MAb, both EPO and ECP were released. In contrast, incubation of EOSs with anti-IgG MAb induced mainly the release of ECP and not EPO. These results indicate that pharmacologically active mediators can be released by EOSs from allergic and nonallergic patients on immunoglobulin-dependent activation. The results also confirm the hypothesis of a selective release of the various granule proteins and raise the question of transduction signals delivered by the three Fc receptors (Fc epsilon R, FC alpha R, and FC gamma R) present on human EOSs.

Allergens↗

PubMed1991

Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction.

The late asthmatic reaction (LAR), consecutive to bronchial allergen challenge, is characterized both by the influx of various cells in proximal and distal airways and by the enhancement of bronchial hyperresponsiveness. However, the exact conditions for the development of the inflammatory reaction during the LAR remain to be specified. Since monokines play a key role in inflammatory processes, particularly in the lung, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin; 1-beta (IL-1-beta) and interleukin-6 (IL-6) by alveolar macrophages (AM), collected 18 to 20 hours after exposure to allergen, was evaluated in 15 allergic subjects with asthma submitted to a challenge test with Dermatophagoides pteronyssinus (N = 6) or with wheat flour (N = 9) and in three healthy subjects. After bronchial provocation test, four patients presented no bronchial response (group 1), and six patients, a single early reaction (group 2). In contrast, five patients developed successively an immediate plus a late response (group 3). The monokine production was compared to that from nine allergic subjects with asthma studied at baseline (group 0) and from 11 unchallenged healthy subjects (control subjects). Measurements of cytokines were evaluated for TNF-alpha and IL-1-beta by a specific immunoradiometric assay, whereas IL-6 levels were appreciated by the proliferation of 7TD1 cells. No detectable amounts of TNF-alpha, IL-1-beta, and IL-6 were in bronchial alveolar lavage fluid, even after a tenfold concentration. In contrast, a significant increase of TNF-alpha (10,642 +/- 3127 U/ml) and IL-6 (1250 +/- 427 U/ml) concentrations was noted in AM supernatants from patients exhibiting an LAR (group 3) compared to cells recovered from groups 2, 1, and 0 and to challenged or unchallenged control subjects (805 +/- 244, 995 +/- 521, 1269 +/- 524, 688 +/- 85, and 445 +/- 74 pg of TNF-alpha per milliliter, respectively; 190 +/- 64, 114 +/- 91, 242 +/- 95, 80 +/- 9, and 54 +/- 19 U/ml of IL-6 per milliliter, respectively). No modification of IL-1-beta contents could be detected between the different groups. A significant correlation was detected between concentrations of TNF and IL-6 (r = 0.92; p less than 0.001). These results demonstrate TNF-alpha and IL-6 secretion by AM consecutively to the development of LAR in allergic subjects with asthma, confirming that AMs are activated after allergen challenge.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1991

Potential implication of endothelial cells in bronchial asthma.

Inflammatory cells like eosinophils, neutrophils or mononuclear phagocytes have long been recognized as essential components in the pathophysiology of asthma. After recruitment in situ and subsequent activation, they are considered as responsible for epithelial and submucosal bronchial alterations. However, to access to the inflammatory site, these cells have to cross the endothelial wall, suggesting so a potential implication of endothelial cells (EC) in bronchial asthma. To test this hypothesis, we studied in a first step the modulation of vascular adhesions like intercellular adhesion molecule-1 (ICAM-1) on EC: supernatants of alveolar macrophages (AM) recovered by bronchoalveolar lavage in patients exhibiting a late asthmatic reaction, induced an enhanced expression of ICAM-1 on EC preparations; increase of ICAM-1 was clearly correlated to amounts of tumor necrosis factor-alpha (TNF alpha) present in AM supernatants, as shown by inhibition experiments with anti-TNF alpha antiserum. The second way to explore the possible role of EC in asthma was the detection of autoantibodies to EC in various allergic disorders: antibodies against a 120-kD EC antigen in patients with allergic granulomatosis and angiitis, antibodies towards a 55-kD component, common to human EC and platelets in patients with severe asthma, namely characterized by their corticosteroid dependence or by aspirin-induced intolerance. So our data suggest that bronchial asthma might result from either EC activation, through the induction of surface adhesion molecules or from an autoimmune process involving EC antigens.

Adolescent↗

PubMed1991

Increased TNF-alpha secretion by alveolar macrophages from patients with rheumatoid arthritis.

Tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) production by alveolar macrophages (AM) was evaluated in 17 rheumatoid arthritis (RA) patients without interstitial lung disease (ILD, Group 1) and 14 RA patients with clinical ILD (Group 2) in comparison with 10 control subjects. AM after recovery by bronchoalveolar lavage were selected by adherence, and then supernatants were collected after 3 or 24 h of culture. Results showed no modification of IL-1 synthesis in either group of RA patients. Spontaneous TNF production was significantly increased in Group 2 (2.5 +/- 0.5 ng/ml) as well as in Group 1 (2.4 +/- 0.4 ng/ml) compared with control subjects (0.43 +/- 0.1 ng/ml, p less than 0.001). In addition, AM from patients untreated or treated exclusively by nonsteroidal antiinflammatory drugs produced similar levels of TNF, whereas those receiving corticosteroids, second-line drugs (such as sulfasalazine, aurothiomalate, and methotrexate), or the combination of both therapy regimens released significantly less TNF. Interestingly, TNF was not different in both groups, but Group 2 had a markedly increased ratio of local immune complex to albumin in bronchoalveolar lavage fluid (0.47 +/- 0.12 versus 0.07 +/- 0.02 in Group 1; p less than 0.002). TNF thus appears an additional component of RA subclinical alveolitis in RA, but its prognostic value and its precise role in lung damage remain to be determined. Development of ILD requires certainly complex interactions of synergistic factors, possibly including local immune complexes detected in BAL fluids.

Antigen-Antibody Complex↗

PubMed1991

Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust.

Following our previous demonstration of cytokine secretion by alveolar macrophages (AM) from coal miners and from patients with coal workers' pneumoconiosis, we investigated the effect of in vitro exposure to coal dust and to its silica content on tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 production by normal human AM. TNF and IL-1 beta concentrations were estimated by a specific radioimmunoassay, while IL-6 levels were evaluated by the proliferation of 7TD1 cells. After 24-h culture, coal dust triggered a significant release of TNF and IL-6 at the dose of 0.1 mg/ml and more obviously at 1 mg/ml in comparison with titanium dioxide (TiO2), used as a biologically inert control dust (with 1 mg/ml of dust: 3,526 +/- 3,509 versus 330 +/- 138 pg TNF/ml and 224 +/- 74 versus 72 +/- 34 U IL-6/ml, respectively; P less than 0.01 in both cases). After 3-h culture, a significant TNF secretion as well as an increased TNF mRNA expression were also detected for AM stimulated by coal dust at variance with TiO2. In contrast, no modification of IL-1 beta concentration could be evidenced in AM exposed to coal dust, although we detected an increased expression of specific mRNA expression. In order to define the role of silica among the main components of coal dust in AM activation, we evaluated the effect of silica (alpha-quartz, 30 micrograms/ml, which is the concentration and the type of silica present in our coal dust) alone or mixed with TiO2 (1 mg/ml) on monokine production.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

PubMed1991

Metastatic prostatic adenocarcinoma-diagnosed by bronchoalveolar lavage and tumour marker determination.

We report a patient who presented with a diffuse interstitial lung disease in whom clinical and radiologic investigation led to the suspicion of lymphangitis carcinomatosa. Bronchoalveolar lavage (BAL) was performed and revealed the presence of prostatic specific antigen (PSA) positive cells. A prostatic needle aspiration confirmed the diagnosis of adenocarcinoma. This case demonstrates the value of tumour marker determination in BAL.

Adenocarcinoma↗

PubMed1991

[Study of high-resolution thoracic computerized tomography and bronchoalveolar lavage in 36 patients presenting with systemic disease and a normal thoracic radiography].

Systemic diseases such as scleroderma (ScI), rheumatoid polyarthritis (PR), Gougerot-Sjögren Syndrome (GS) have a well known propensity for the lungs. Previous studies have shown evidence of disturbed alveolar cell repair as evidence of a sub-clinical alveolitis. The significance of such cases of latent alveolitis remains to be specified. To determine if latent alveolitis was associated with interstitial chest disease which was undetectable by chest X-ray, 36 consecutive patients had an BAL and a high resolution computered tomographic examination (HRTC) (Scl: n = 21; PR: n = 9; GS: n = 6). The patients had normal respiratory function and chest X-ray was normal. Our results showed 17 out of 36 (47%) with a latent alveolitis (the percentage of lymphocytes and of alveolar polymorpho-nuclear neutrophils was superior or equal to 18 and 4% respectively) (Scl: 12/21; PR: 1/9; GS: 4/6). In the cases of scleroderma a neutrophil alveolitis was predominant (9/12) and was associated in 2 cases with a honeycomb lung and evidence of fibrotic lesions using TDM-HR. Those examinations using HRTC which were normal were equally associated with a latent alveolitis (Scl: 6/12; PR: 1/6; GR: 4/5). These results suggest that the alveolitis can preceed the anatomical damages. These results need to be confirmed in a larger series and the value of early treatment should be evaluated.

Adolescent↗

PubMed1991

Neutrophil-endothelial cell interaction: evidence in vitro for a regulation by endothelial cells of neutrophil functions.

The purpose of this study was to investigate a possible relationship between human umbilical vein endothelial cells (EC) triggered by ionophore A23187 at different doses (0.5-2.5 microM) and polymorphonuclear neutrophils (PMN). EC supernatants were shown to contain neutrophil chemoattractant activity (NCA) and in parallel a factor inducing an inhibition of PMN chemiluminescence (PMN CL). Supernatants obtained from EC triggered by A23187 exhibited a high level of NCA (73 +/- 5 PMN.hpf-1 compared to 21 +/- 4 PMN.hpf-1 in untreated EC supernatants, p less than 0.01). This NCA was independent from arachidonic acid metabolites, since indomethacin and nordi-hydroguaiaretic acid failed to suppress the chemotactic activity. Using gel filtration chromatography (AcA 54) the NCA was recovered in a single peak of apparent molecular weight of 37,000 +/- 4,000 daltons. Checkerboard analysis indicated that NCA exhibited both chemotactic and chemokinetic activities. In addition, supernatants of A23187-stimulated EC, and at a lesser degree, supernatants of unstimulated EC, inhibited PMN CL induced by N-formyl-Methionyl-Leucyl-Phenylalanine (61% inhibition, p less than 0.05), and by A23187 itself (80% inhibition, p less than 0.01), but not that induced by phorbol-myristate-acetate. Indomethacin and protamine sulphate did not modulate this inhibitory activity. By contrast, EC-derived inhibitory activity was inhibited (50%) by an adenosine antagonist (8-phenyltheophylline), indicating a participation of adenosine in this inhibitory activity of PMN CL. These data suggest the possibility that activated endothelial cells could both enhance PMN migration and protect themselves against potential damaging effects of oxygen metabolites produced by PMN, particularly during transvascular migration.

Calcimycin↗