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A Pforte

Publications and source records attributed to A Pforte.

36 records · Page 2Linked to original sources

Expression of CD14 correlates with lung function impairment in pulmonary sarcoidosis.

CD14 expression on alveolar macrophages (AM) was studied in patients with sarcoidosis using immunocytochemistry and cytometric analysis. Compared with healthy control donors, patients had elevated percentages of CD14-positive AM (22 percent vs 34 percent), and the antigen density was threefold higher (92 vs 297 channels). Furthermore, soluble serum CD14 (ssCD14) was significantly elevated in patients with sarcoidosis with an average of 5.3 +/- 1.6 mg/L vs 3.2 +/- 0.7 mg/L in healthy control subjects. Follow-up of one patient, whose lung function test results improved during therapy with corticosteroids, revealed a concomitant decrease of CD14 staining on AM and of ssCD14. Statistical analysis revealed a negative correlation between CD14 expression on AM and PO2 at rest (p = 0.0005), and after labor (p = 0.02). Levels of ssCD14 gave a positive correlation to reduction of Dco (p = 0.006) and VC (p = 0.05). These data suggest that CD14 expression is related to severity of disease and that it may be useful for monitoring in sarcoidosis.

Adult↗

[Bronchial asthma].

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Activities of Daily Living↗

The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients.

Staining with CD14 and CD16 monoclonal antibodies will identify two monocyte subpopulations in human blood: a major population of regular monocytes, which strongly expresses the CD14 antigen (CD14++), and a minor population with weak expression of CD14 and expression of the CD16 antigen (CD14+/CD16+ cells). As shown herein, the latter cells account for 45 +/- 22 cells/microL and 9% +/- 5% of the monocytes in healthy control donors (n = 35). In septicemia patients, the CD14+/CD16+ cells can become a major population, with more than 50% of all monocytes in 3 of 18 patients and with more than 500 cells in 4 of 18 cases. There was no correlation of CD14+/CD16+ cells to any clinical parameter except for CD14+/CD16+ percentage and body temperature (P = .013). The CD14++ regular monocytes showed a substantial decrease in CD14 antigen density in 9 of 11 patients. Three-color immunofluorescence shows that the CD14+/CD16+ monocytes in septicemia patients when compared with the CD14++ monocytes exhibit a higher level of class II antigen and a lower level of CD11b and CD33 antigens, consistent with a more mature nature of the CD14+/CD16+ cells. Levels of interleukin-6 (IL-6) were increased in septicemia patients; 3 of 5 patients with high numbers of CD14+/CD16+ cells (> 200/microL) had high levels of IL-6 (> 250/U/mL). These data suggest that septicemia may lead to substantial changes in blood monocyte composition and this may be related to elevated levels of cytokines such as IL-6.

Adult↗

The novel subset of CD14+/CD16+ blood monocytes exhibits features of tissue macrophages.

The CD14+/CD16+ cells account for about 10% of all blood monocytes. They are characterized by a low level expression of the CD14 molecule and a high level expression of the CD16 (Fc gamma R III) molecule. Polymerase chain reaction analysis of mRNA prevalence in CD14+/CD16+ cells (compared to the regular CD14++ blood monocytes) demonstrates low levels of CD14 transcripts and high levels of CD16 transcripts, suggestive of a transcriptional control for both of these proteins. Analysis of additional cell surface molecules in three-color immunofluorescence reveals that CD14+/CD16+ cells express the Fc gamma R II in all, and Fc gamma R I and ICAM-1 in some donors. Furthermore, class II antigens are expressed at fourfold higher levels, while both, CD11b and CD33 cell surface proteins, are decreased by a factor of two. Transcript levels were reduced in CD14+/CD16+ cells for all three cell surface molecules. Since these phenotypic markers of the CD14+/CD16+ blood monocytes are reminiscent of tissue macrophages, we performed a comparative analysis with alveolar macrophages (AM). These cells are similar to the CD14+/CD16+ monocytes in that they show low levels of CD14 and strong expression of CD16. Furthermore, similar to the CD14+/CD16+ cells, the AM also exhibit higher levels of class II and lower levels of CD11b and CD33 when compared to the regular CD14++ blood monocytes. In vitro induction of maturation of blood monocytes by 5 day culture of peripheral blood mononuclear cells in 10% human serum will result in decreased CD14 and increased CD16 cell surface expression on the monocyte derived macrophages. At the same time, these cells acquire increased levels of class II and decreased levels of CD11b and CD33. Taken together, these data show that CD14+/CD16+ monocytes, while still in circulation, have acquired features in common with mature tissue macrophages.

Antigens, CD↗

Expression of the adhesion molecule ICAM-1 on alveolar macrophages and in serum in extrinsic allergic alveolitis.

ICAM-1 expression was studied on alveolar macrophages (AM) in extrinsic allergic alveolitis (EAA) using immunocytochemistry and cytometry. Compared to control donors, EAA patients had higher percentages of ICAM-1+ AM (75% vs. 30%) and the antigen density was more than sixfold higher (673 vs. 103 channels). Levels of soluble serum ICAM-1 were found increased in EAA patients with an average of 866.2 +/- 300 ng/ml versus 394.8 +/- 110 ng/ml in controls. These data are consistent with the concept that antigen contact upregulates ICAM-1 expression on AM in EAA followed by shedding and an increase in serum sICAM-1.

Adult↗

Concomitant modulation of serum-soluble interleukin-2 receptor and alveolar macrophage interleukin-2 receptor in sarcoidosis.

Interleukin-2 receptor (IL-2R) expression on bronchoalveolar lavage (BAL) cells was studied in patients with sarcoidosis using immune cytochemistry and cytometric analysis. A low percentage of alveolar lymphocytes (AL) was found positive for IL-2R, with 7% in patients with impaired lung function and 6% in patients with normal lung function (0.4% in control subjects). Expression of IL-2R on alveolar macrophages (AM) was considerably higher, with 25% in patients with lung function impairment compared with 14% in patients without lung function impairment (1.5% in control subjects). Serum-soluble IL-2R (ssIL-2R) was significantly elevated only in patients with impaired lung function (140.0 pM), but not in patients with normal lung function (52.2 pM; control subjects, 40.0 pM). These elevated levels of ssIL-2R positively correlated with the percentage of IL-2R positive AM (p < 0.001). Immunosuppressive treatment in three patients resulted in a decrease of IL-2R+ AM and in a decrease of ssIL-2R, whereas IL-2R+ AL were unaffected. The positive correlation and the concomitant decrease of IL-2R+ AM and ssIL-2R are consistent with the idea that in sarcoidosis with clinically apparent lung involvement, elevated levels of ssIL-2R may be derived from AM and may thus be a useful indicator of the degree of activation of these cells.

Adult↗

Increased expression of the monocyte differentiation antigen CD14 in extrinsic allergic alveolitis.

Expression of the CD14 antigen was studied on alveolar macrophages in extrinsic allergic alveolitis (EAA), using immunocytochemistry and cytometry. Compared to control donors, EAA patients had higher percentages of My4 positive cells (40 versus 22%), and the antigen density was fourfold higher (410 versus 92 channels). Levels of soluble CD14 (sCD14) in serum were found to be increased in EAA patients with an average of 4.6 +/- 1.5 micrograms.ml-1 compared to 3.2 +/- 0.7 micrograms.ml-1 in controls. Follow-up of patients with antigen avoidance revealed a concomitant decrease of CD14 staining of alveolar macrophages (AMs) and of sCD14 in serum, whilst allergen exposure induces both parameters. These data are consistent with the concept that antigen contact upregulates CD14 expression on AMs in EAA, followed by shedding and increase of sCD14 in serum.

Adult↗

[Detection of the IgE receptor CD23 in sarcoidosis].

In 30 sarcoidosis patients the soluble IgE receptor sCD23 was determined. Compared to healthy controls a marked increase of this molecule could be detected in serum (4.9 versus 0.9 ng/ml). In 19 patients who underwent bronchoscopy a strong expression of CD23 on alveolar macrophages could be demonstrated in immunochemistry compared to healthy controls (40.8 versus 12.6%). Determination of total IgE and anti-IgE antibodies did not allow discrimination between healthy controls and sarcoidosis patients. Our data suggest that alveolar macrophages are an important source for soluble CD23 in serum. CD23 expression might reflect functional activation of macrophages since our results do not appreciate a role for IgE-related reactions in sarcoidosis.

Adult↗

Proliferating alveolar macrophages in BAL and lung function changes in interstitial lung disease.

In interstitial lung disease, the number of alveolar macrophages (AMs) can be increased. This may be caused by recruitment of precursor cells from peripheral blood and/or local proliferation in the lung. We therefore analysed proliferation, by studying both the expression of the nuclear proliferation antigen, Ki67, and the deoxyribonucleic acid (DNA) content, using the Feulgen reaction followed by cytometry. The patients had interstitial lung disease, i.e. sarcoidosis (n = 20), extrinsic allergic alveolitis (n = 20), idiopathic lung fibrosis or lung involvement in collagen-vascular disease (n = 19). In all patient groups there was a significant increase in proliferating AMs compared to healthy controls (4.2 versus 1.4% Feulgen, 2.1 versus 0.5% Ki67), with a significant correlation between these two parameters. A positive correlation was also found in bronchoalveolar lavage (BAL) between numbers of lymphocytes and proliferating cells in sarcoidosis and in fibrosis. In fibrosis, numbers of eosinophils and proliferating cells were also positively correlated. Our main finding was, however, a positive correlation between numbers of proliferating cells (Feulgen) and lung function parameters, especially vital capacity and oxygen tension (PO2) at rest, in patients with sarcoidosis and lung fibrosis. By contrast, in extrinsic allergic alveolitis, no correlation could be observed between proliferating cells and cell population or lung function. Our results suggest that local proliferation of macrophages is an important element in interstitial lung disease.

Adult↗

Small (CD14+/CD16+) monocytes and regular monocytes in human blood.

Compared to the obvious phenotypic and functional heterogeneity of tissue macrophages, little information is available on subsets of blood monocytes. We have employed two-color immunofluorescence and flow cytometry for the definition of regular and small monocytes, the latter characterized by the low-density expression of CD14 and the strong expression of the CD16 (Fcy-RIII) antigen. These cells comprise 15% of the blood monocytes and they appear to be similar in phenotype to the alveolar macrophage. The CD14+/CD16+ small monocytes can perform phagocytosis and they produce reactive oxygen, while their capacity for cytokine production is strongly reduced when compared to regular monocytes. At this point it is still unclear as to whether the CD14+/CD16+ small monocytes comprise a specific level of activation or differentiation or a distinct sublineage of human blood monocytes.

Antigens, CD↗

Expression of the Fc-receptor for IgE (Fc epsilon RII, CD23) on alveolar macrophages in extrinsic allergic alveolitis.

Expression of the Fc receptor for IgE (Fc epsilon R) was analyzed on alveolar macrophages (AM) in 10 patients with extrinsic allergic alveolitis (EAA) compared with 10 patients with sarcoidosis and to 6 apparently healthy controls. By using the anti-Fc epsilon RII mAb M-L25 in immunocytochemistry experiments, we found that greater than 60% of AM in 10 of 10 patients with EAA were strongly positive, as evidenced by visual analysis in light microscopy and by cytometry. By contrast, no significant staining was detected in sarcoidosis or in controls with either method. Similar results were obtained when Fc epsilon R were identified with preformed immune complexes consisting of NIP-specific human/mouse chimeric IgE antibody plus NIP-ovalbumin. Furthermore, greater than 60% of AM in patients with EAA stained positive for IgE, demonstrating that endogenous IgE is bound to the AM. Our data suggest that IgE antibodies bound to Fc epsilon RII on AM may be involved in pathophysiology of extrinsic allergic alveolitis by activation of the AM after binding of allergen to the cell surface IgE. Furthermore, with the clearcut pattern of Fc epsilon RII expression in extrinsic allergic alveolitis it may be possible to use CD23 antibodies for differential diagnosis of inflammatory lung disease.

Adult↗

[Long-term follow-up of 52 endoluminal irradiated patients with central lung tumors].

The results of a prospective follow-up study comprising 52 patients with central tumours of the lung submitted to endoluminal irradiation are reported. Additional external irradiation was possible in 30 patients (group A), but not in 22 patients (group B). Satisfactory immediate results were observed, together with a one-year survival rate of 39.3% (group A) and 12.5% (group B).

Aged↗

A role for IgE in extrinsic allergic alveolitis?

Receptors for the Fc portion of immunoglobulin E (IgE; CD23) can be detected on the surface of alveolar macrophages (AM) in extrinsic allergic alveolitis (EAA), using monoclonal antibodies in immunocytology. More than 50% of AM were positive in 16 of the 20 patients reported here, while the remaining 4 had 11-47% positive cells. Staining with anti-IgE antibody can, in addition, demonstrate endogenous IgE bound to the AM. This suggests that IgE might be involved in the process. Since IgE-mediated asthma is associated with bronchoconstriction, we asked whether EAA patients do in fact exhibit an obstructive component. In 3 out of 10 patients we did indeed find clearly increased airway resistance (greater than 30 kPa x s x l-1). These findings are consistent with the observation of immediate bronchoconstriction observed in some patients upon allergen challenge. Since only 1 of the 20 patients studied was a smoker, and since in the literature the majority of reported cases of EAA are in nonsmokers, we speculate that smoking may interfere with immunological processes leading to EAA.

Adult↗