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M Gjomarkaj

Publications and source records attributed to M Gjomarkaj.

12 recordsLinked to original sources
PubMed1999

IL-4 and IgE-anti-IgE modulation of 15(S)-hydroxyeicosatetraenoic acid release by mononuclear phagocytes.

BACKGROUND: IL-4 modulates the synthesis of IgE, the expression of CD23, and the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE). OBJECTIVE: We evaluated the release of 15(S)-HETE by IL-4-stimulated monocytes and verified whether the observed increase in 15(S)-HETE release after passive sensitization and anti-IgE challenge of IL-4-treated monocytes was secondary to an increased CD23 expression. METHODS: Human monocytes were incubated for 24, 48, and 72 hours with IL-4 (10 ng/mL) with or without an IgE-anti-IgE stimulation. We evaluated CD23 expression by immunocytochemistry and 15(S)-HETE release by HPLC and RIA. To prove that the increase in 15(S)-HETE release was due to the effect of IL-4 on CD23, we performed experiments with an anti-CD23 blocking mAb. RESULTS: CD23 expression and 15(S)-HETE release were significantly increased by IL-4, reaching a peak after 72 hours (P <.02). After passive sensitization with human IgE and anti-IgE challenge, IL-4-stimulated monocytes released higher amounts of 15(S)-HETE than IL-4-unstimulated monocytes (P <.02). Pretreatment with the anti-human B-cell CD23 MHM6 mAb caused a dose-dependent inhibition of 15(S)-HETE release. CONCLUSIONS: This study shows that immunologic challenge of IL-4-treated, passively sensitized monocytes results in a CD23-dependent additional increase of 15(S)-HETE release, indicating the presence of a synergistic effect of IL-4 on CD23 expression and 15(S)-HETE production.

Antibodies, Anti-Idiotypic↗
PubMed1999

Interleukin-8 induces lymphocyte chemotaxis into the pleural space. Role of pleural macrophages.

The pleural space is a potential compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells in a number of respiratory diseases. In an attempt to understand one aspect of the inflammatory process in the pleural space, we compared the responses in three different diseases (congestive heart failure [CHF], tuberculosis [TB], and cancer). Large concentrations of interleukin-8 (IL-8) were detected in cancer and TB effusions, but not in CHF. Surprisingly, the concentration of IL-8 correlated best with lymphocyte recruitment and not with neutrophil recruitment. Pleural fluid from cancer and TB patients was chemotactic for lymphocytes, and this activity was partly blocked by an anti-IL-8 antibody in cancer and completely blocked in TB. To determine whether there was the potential for a chemotactic gradient into the pleural space, pleural effusion cells were analyzed for the expression of IL-8. Cells in the effusions of cancer patients expressed IL-8, whereas IL-8 could not be detected from the cells of TB and CHF effusions. To explore the possible role of pleural macrophages in the regulation of IL-8, pleural effusion cells were treated with culture supernatants from stimulated pleural macrophages. Stimulated pleural macrophages were able to induce expression of messenger RNA (mRNA) for IL-8 and IL-8 protein production, and this activity was abrogated by blocking tumor necrosis factor-alpha. These findings suggest that soluble IL-8 is an important factor for the recruitment of lymphocytes into the pleural space, and that this cytokine is produced by both pleural structural and cancer cells after their activation by macrophage-derived, cytokine-mediated signals.

Adult↗
PubMed1999

Phenotypic and functional characterization of normal rat pleural macrophages in comparison with autologous peritoneal and alveolar macrophages.

Pleural mononuclear phagocytes (PleMP) were isolated from normal rats by pleural lavage and compared with autologous peritoneal (PerMP) and bronchoalveolar mononuclear phagocytes (BAMP) isolated by peritoneal and bronchoalveolar lavage, respectively. The phagocytic activity of PleMP, PerMP, and BAMP, evaluated by testing their ability to ingest latex beads, was lower for PleMP and PerMP than for BAMP. The phenotype of PleMP, PerMP, and BAMP was characterized by immunocytochemical staining with a panel of monoclonal antibodies (mAbs). As expected, PleMP, PerMP, and BAMP did not react with OX19, OX33, ED5, MOM/3F12/F2, and anticytokeratin mAbs, specific for T lymphocytes, B lymphocytes, dendritic cells, granulocytes, and epithelial/mesothelial cells, respectively. Moreover, PleMP and PerMP populations were highly enriched with OX6-, OX42-, ED7-, and ED8-positive MP, whereas BAMP population was enriched with ED1- and ED9-positive cells. To test the ability of PleMP, PerMP, and BAMP to function as accessory cells (AC), mitomycin C-treated MP were used as stimulatory cells in mixed leukocyte reaction experiments, using allogeneic T cells as responders. 3HdTR incorporation by T cells was assessed as an index of AC function. PleMP and PerMP were more potent AC than BAMP. Moreover, when cultured together with autologous pulmonary interstitial dendritic cells, PleMP and PerMP exerted a more potent ability to stimulate T-cell proliferation than did BAMP. To investigate the capacity of MP to function as bactericidal and fungicidal cells, we tested their ability to kill Escherichia coli and Cryptococcus neoformans, respectively. PleMP and PerMP were less potent bactericidal and fungicidal cells than BAMP. The results of this study demonstrate that PleMP isolated from normal rat pleural space are functionally and phenotypically different from BAMP but similar to PerMP, and suggest that these cells might play an important role in cell-mediated immune reactions in the pleural space.

Animals↗
PubMed1998

Monocytes.

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Chemokines↗
PubMed1997

Dendritic cells with a potent accessory activity are present in human exudative malignant pleural effusions.

Dendritic cells are human leucocyte antigen (HLA)-DR positive accessory cells, that play a critical role in the development of cell-mediated immune reactions. Since the pleural space is frequently involved in cell-mediated immune reactions, we sought to isolate dendritic cells from pleural fluid. Pleural effusion mononuclear cells (PEMCs) were obtained by Ficoll centrifugation of exudative pleural effusions recovered from 19 patients with malignant pleurisy. After double-step adherence, firmly-adherent mononuclear cells (FAMs) and loosely-adherent mononuclear cells (LAMs) were recovered. The latter cells were centrifuged on a bovine plasma albumin gradient to obtain a loosely-adherent low density fraction. Nonadherent cells were rosetted with sheep red blood cells (SRBC) to obtain a nonadherent nonrosetting (NANR) cell fraction. Mitomycin C-treated PEMCs, NANRs, FAMs, and LAMs served as stimulatory cells in mixed leucocyte reaction experiments. 3H-thymidine incorporation by purified normal allogeneic blood T-lymphocytes was assessed as an index of accessory cell function. The phenotype of NANR, FAM and LAM cells was characterized using single and double stainings with a panel of monoclonal antibodies (MoAbs). Accessory cell (AC) activity (counts per minute (cpm) x 10(3)(+/-SE); 2.5 x 10(4) AC x well(-1) of LAM (148+/-24) and NANR (108.4+/-11.2) was greater than that observed for FAM (59.3+/-9.4) and for unfractioned PEMC (13.8+/-4.9). The FAM fraction was virtually entirely composed of CD68+ HLA-DR+ mononuclear phagocytes. NANR and LAM contained 51+/-12% and 65+/-6% HLA-DR+ cells, respectively, and most HLA-DR positive cells were negative for CD3, CD19, and CD68, markers for T-, B-lymphocytes and mononuclear phagocytes. Moreover, both NANR and LAM fractions contained significant numbers of cells bearing the RFD1 surface marker, expressed on dendritic cells. These results suggest that dendritic cells are present in exudative pleural effusions, and that they may be involved in the development of cell-mediated immune reactions in the pleural space.

Aged↗
PubMed1996

ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines on the interaction with LAK cells.

Intercellular adhesion molecule-1 (ICAM-1) expression by tumour cells may be involved in their interaction with defensive cells. In this study the surface ICAM-1 expression and soluble ICAM-1 (sICAM-1) production by five small cell lung cancer (SCLC) and five non-SCLC (NSCLC) cell lines was investigated. In addition, the effects of ICAM-1 upregulation by cytokines on the adhesion of lung cancer cells to allogeneic lymphokine-activated killer (LAK) cells and susceptibility to LAK cytotoxicity was also evaluated. ICAM-1 expression was assessed by flow cytometry. Soluble ICAM-1 release was measured by enzyme-linked immunosorbent assay (ELISA). Interaction with LAK cells was tested by adhesion and cytotoxicity assays. At baseline, SCLC lines did not express ICAM-1, while 4 of the 5 NSCLC lines expressed ICAM-1. ICAM-1 expression was induced by interferon-gamma (IFN-gamma) in 4 of the 5 SCLC lines and upregulated in 1 of the 5 NSCLC lines. ICAM-1 expression was induced by tumour necrosis factor-alpha (TNF-alpha) in 1 of the 5 SCLC lines (National Cancer Institute (NCI) H211), and upregulated in 2 of the 5 NSCLC lines (NCI H460 and NCI H838). Among the latter lines, one (NCI H838) released significant amounts of sICAM-1. Adhesion to LAK cells and susceptibility to LAK cytotoxicity were significantly higher in TNF-alpha-treated NCI H460 and NCI H211 cells, compared to untreated NCI H460 and NCI H211 cells. In contrast, no difference in adhesion to LAK cells and susceptibility to LAK cytotoxicity was detected between baseline and TNF-alpha-treated NCI H838 cells. Intercellular adhesion molecule-1 surface expression and soluble intercellular adhesion molecule-1 release may play an important role in interactions between lymphokine-activated killer cells and lung cancer cells.

Antineoplastic Agents↗
PubMed1994

Mononuclear cells in exudative malignant pleural effusions. Characterization of pleural phagocytic cells.

The aims of this study were to develop a methodology for the isolation of highly enriched mononuclear phagocyte populations from exudative malignant pleural effusions (EMPE) and to characterize the phenotype and functional properties of these cells. Pleural effusion mononuclear cells (PEMC) were isolated by Ficoll centrifugation of EMPE and transudative pleural effusions and allowed to adhere to plastic for 1 h to obtain a pleural effusion mononuclear adherent cell (PEMAC) fraction. Only 66.0 +/- 4.2 percent of PEMAC ingested latex particles, indicating that a significant proportion of PEMAC were not phagocytic cells. Latex-positive PEMAC had the morphologic appearance of macrophages and stained positive (97.3 +/- 4.3 percent) with the anti-CD68 monoclonal antibody (MoAb), specific for macrophages. Conversely, latex-negative PEMAC (34.0 +/- 4.1 percent of PEMAC) did not react with the anti-CD68 MoAb and stained with anti-CD3 (34.7 +/- 10.7 percent) and anticytokeratin (50.5 +/- 16.4 percent) MoAbs, indicating that T cells and mesothelial cells were present in the PEMAC fraction. To improve the purification of pleural macrophages, PEMAC were cultured for an additional 18 h and the cells that remained adherent after this period constituted the firmly adherent mononuclear cell (FAMC) fraction. Nearly 90 percent of FAMC ingested latex particles and were CD68-positive. Virtually all FAMC were CD3-negative and cytokeratin-negative. Similar percentages of FAMC from EMPE and transudative effusions expressed the monocyte-lineage markers CD11b and CD14, suggesting that the proportion of monocyte-like mononuclear phagocytes in the pleural space is not increased during local tumor-associated inflammatory responses. The FAMC from EMPE (1) expressed HLA-DR antigens, (2) released interleukin 1 (IL-1) beta and tumor necrosis factor (TNF) alpha, and (3) stimulated allogeneic T-lymphocyte proliferation. The results of this study suggest that pleural mononuclear phagocytes may be involved in tumor-associated inflammatory reactions in the pleural compartment by stimulating the proliferation of other inflammatory cells and by releasing inflammatory cytokines.

Aged↗
PubMed1992

Antitumour activity of mononuclear phagocytes: role of tumour necrosis factor alpha.

Tumour necrosis factor alpha (TNF) is a cytokine produced by mononuclear phagocytes (MP) originally discovered for its cytotoxic activity on tumour cell targets. It was subsequently demonstrated that, in addition to its oncolytic potential, TNF exerts a wide variety of activities on the host defensive system against malignancies. This article briefly reviews the current concepts on the role of TNF in the antitumour activity of MP.

Cytotoxicity, Immunologic↗
PubMed1991

Increased expression of leukocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) by alveolar macrophages of patients with pulmonary sarcoidosis.

Leukocyte function associated antigen-1 (LFA-1) and its ligand intercellular adhesion molecule-1 (ICAM-1) are cell adhesion molecules that play an important role in the capacity of monoculear phagocytes (MPs) to present antigens to T lymphocytes. Since in pulmonary sarcoidosis (PS) this capacity is increased at sites of disease activity, we studied the expression of LFA-1 and ICAM-1 on peripheral blood monocytes (BMs) and alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) from normal subjects (n = 7) and patients with PS (n = 14). To accomplish this, immunocytochemical stainings were made on cytocentrifuge preparations using anti-LFA-1 (anti-CD 11a) and anti-ICAM-1 (anti-CD 54) monoclonal antibodies (MoAbs). Normal and sarcoid BMs displayed a high percentage of positivity with both MoAbs with no difference between study groups (LFA-1: control BM 87.8 +/- 8.8 percent; sarcoid BM 84.7 +/- 9.5 percent; ICAM-1: control BM 80.8 +/- 10 percent; sarcoid BM 88.0 +/- 4.2 percent; p = NS for all comparisons). In both groups the percentage of cells expressing LFA-1 and ICAM-1 molecules among AMs was lower than among autologous BMs (LFA-1: control AM 46.5 +/- 13.2 percent, p less than 0.001 vs control BM; sarcoid AM 64.2 +/- 15.9; p less than 0.001 vs sarcoid BM) (ICAM-1: control AM 42.7 +/- 8.5 percent, p less than 0.001 vs control BM; sarcoid AM 72.1 +/- 10.6, p less than 0.001 vs sarcoid BM). AMs from patients with PS showed a higher degree of positivity for LFA-1 and ICAM-1 than normal AMs (p less than 0.02 and p less than 0.001, respectively). The positivity for LFA-1 and ICAM-1 molecules on sarcoid AMs was not correlated with the positivity for two different BM-associated markers (ie, the CD 11b and the CD 14 molecules) and was not correlated with the percentage of T lymphocytes in BAL, selected as a marker of the intensity of the alveolitis. These results suggest that the increased ability of sarcoid AMs to induce the proliferation of T lymphocytes may be related, at least in part, to the increased expression of LFA-1 and ICAM-1 molecules on their surfaces.

Antigen-Presenting Cells↗
PubMed1989

Lung compartmentalization of increased TNF releasing ability by mononuclear phagocytes in pulmonary sarcoidosis.

The TNF is a monokine with cytotoxic and tumor-necrosing activities; in addition, TNF may play a role in inflammatory processes. The present study evaluates spontaneous and LPS-mediated release of TNF by AMs and autologous peripheral BMs of normal subjects and patients with pulmonary sarcoidosis. A recently developed cytotoxicity assay, specific for detection of TNF activity, was applied. This study demonstrates that (1) unstimulated mononuclear phagocytes released low levels of TNF with no differences between groups; (2) when effector cells were stimulated with LPS, AMs from patients with active pulmonary sarcoidosis released more TNF than AMs recovered from normal subjects and from patients with inactive disease; (3) this increase was compartmentalized to the lungs, since comparisons of TNF production by LPS-stimulated BMs failed to show any difference between study groups. These results suggest that TNF might play a role in the pathogenesis of the alveolitis of pulmonary sarcoidosis.

Adult↗
PubMed1988

Tumor necrosis factor release by pulmonary alveolar macrophages.

Tumor necrosis factor (TNF) is a monokine with cytotoxic and tumor-necrosing activities that may play a role in host defence against malignancies. The aim of the present study was to assess the ability of pulmonary alveolar macrophages (AMs) to release TNF. To accomplish this, a cytotoxicity assay specific for TNF detection was applied, using as targets actinomycin-D-pretreated WEHI 164 murine sarcoma cells. AMs mediated cytotoxicity levels comparable to those mediated by autologous blood monocytes (BMs). In addition, cytotoxicity was accounted for by a soluble factor released by effector cells and was completely inhibited by the addition of anti-TNF antibodies. These results indicate that AMs are able to release TNF. Moreover, since TNF has now been recognized as an important mediator of inflammation, its production by AMs suggests that this monokine might play a role in the pathogenesis of a variety of nonmalignant lung disorders.

Adult↗