PubMed Health⌕ Search

Biomedical subjects

P Pavli

Publications and source records attributed to P Pavli.

28 records · Page 2Linked to original sources
PubMed1995

Evidence for a CD14+ population of monocytes in inflammatory bowel disease mucosa--implications for pathogenesis.

Lipopolysaccharide (LPS) is abundant in the intestinal lumen. CD14 is the receptor for the LPS-LPS binding protein complex, and its presence on mononuclear phagocytes allows cell activation by pg/ml concentrations of LPS. We have shown that the recently recruited blood monocyte in inflammatory bowel disease mucosa is CD14+. This study examined the expression of CD14 on macrophages in inflamed (n = 13) and uninflamed (n = 7) intestine by immunohistochemistry, and on disaggregated lamina propria mononuclear cells (12 from inflamed, 17 from uninflamed intestine) and peripheral blood mononuclear cells (n = 26) by flow cytometry, using a panel of three MoAbs directed against CD14. Immunohistochemistry revealed that 3.7% of macrophages in uninflamed intestine were CD14+, while 25.1% of macrophages in active inflammatory bowel disease expressed CD14 (P < 0.02). Flow cytometry demonstrated that CD14 expression by macrophages from Crohn's disease and ulcerative colitis was augmented significantly (P = 0.02 and P = 0.01, respectively) compared with uninflamed intestine, with a discrete population of macrophages in inflammatory bowel disease, not present in normal intestine, which strongly expressed CD14. The characteristically high levels of CD14 on blood monocytes were unaffected by the presence of intestinal inflammation. Given the exposure of lamina propria cells to LPS present in the lumen of the terminal ileum and colon, the increased numbers of CD14+ macrophages in inflammatory bowel disease may result in greatly increased production of inflammatory mediators, thereby suggesting a mechanism for the perpetuation of mucosal inflammation.

Antigens, CD↗
PubMed1993

Dendritic cells, the major antigen-presenting cells of the human colonic lamina propria.

Induction of T-cell responses requires the recognition of antigen in association with class II major histocompatibility complex (MHC) antigens on specialized antigen-presenting cells. It was previously demonstrated that dendritic cells were the major antigen-presenting cell in the mouse intestinal lamina propria whilst macrophages were shown to be suppressive. The aim of this study was to compare the antigen-presenting cell activity of human colonic dendritic cells with macrophages. Colonic mucosa was removed from 46 specimens resected for cancer and other non-malignant conditions and lamina propria cell suspensions obtained by EDTA treatment followed by enzymatic digestion. Lamina propria cell suspensions, depleted of macrophages by adherence to insolubilized human immunoglobulin and carbonyl iron phagocytosis, were enriched for dendritic cells by density gradient centrifugation. Yields represented 0.9% (range 0.7-1.4%) of the starting cell number and the degree of enrichment was 30-50%. Immunocytochemistry demonstrated high levels of class II MHC antigen expression, but low levels or absent expression of macrophage and other markers. The ultrastructural features of the low-density cell fraction were typical of dendritic cells with cytoplasmic extensions or veils and the absence of phagocytic vesicles. Populations of cells enriched for macrophages were obtained by harvesting the human immunoglobulin-adherent cells. These cells were > 70% positive for macrophage markers using immunocytochemistry. The ability of lamina propria cells to induce primary T-cell activation was assayed using allogeneic peripheral blood T cells as responders in the mixed leucocyte reaction (MLR). When antigen-presenting activity was assessed using the MLR, the stimulatory activity was present in the dendritic cell-enriched fraction, with little activity present in the macrophage fraction. These data indicate that dendritic cells, not macrophages, are the major cell population capable of generating a mixed leucocyte reaction in the human colonic lamina propria.

Cell Adhesion↗
PubMed1992

Pathogenic factors in inflammatory bowel disease. I. Ulcerative colitis.

The identification of the early events occurring in ulcerative colitis may lead to a better understanding of the etiology of this disease. Many observations have now indicated that colonic epithelial abnormalities occur independently of the presence of mucosal inflammation and have suggested that early events are more likely to involve the epithelium than immuno-inflammatory mechanisms. Although a large number of candidate luminal and mucosal mechanisms for injuring the epithelium or modulating its function can be identified, the real reasons why the epithelium is abnormal remain unclear. Mucosal inflammation may well be a secondary phenomenon due to influx into the lamina propria of luminal macromolecules with toxic, antigenic, immunoadjuvant and chemoattractant properties. This pathogenic model offers new areas of focus for research and the potential for novel therapeutic approaches.

Autoimmune Diseases↗
PubMed1992

Pathogenic factors in inflammatory bowel disease. 2. Crohn's disease.

Clues from patient and experimental animal studies suggest that events occurring early in the pathogenesis of Crohn's disease are related to an inability of the immune system to eradicate one or a number of luminal antigens resulting in persistent T cell and macrophage activation. Whether the primary abnormality rests with the nature of the luminal antigen, disturbances of antigen uptake by the mucosa, antigen handling by macrophages, or macrophage-T cell interactions remains unresolved. Given the heterogeneity of clinical presentations and experimental data, Crohn's disease may be a group of disorders associated with a number of primary defects.

Antigens↗
PubMed1990

Isolation and characterization of antigen-presenting dendritic cells from the mouse intestinal lamina propria.

A method was developed for the isolation of antigen-presenting dendritic cells, and macrophages, from mouse intestinal lamina propria and Peyer's patches. Peyer's patches, and the lamina propria of both the small and large intestine, contained cells with potent stimulatory activity in the allogeneic mixed leucocyte reaction. These cells were separated from macrophages by fibronectin adherence and further enriched by density centrifugation. The isolated stimulatory cells expressed high levels of class II major histocompatibility complex (MHC) antigens, and resembled splenic dendritic cells in both morphology and function. Macrophages were recovered from the lamina propria but not Peyer's patches. These cells also expressed class II MHC antigens, but failed to stimulate the mixed leucocyte reaction and, instead, induced indomethacin-sensitive suppression.

Animals↗
PubMed1989

The prevalence of serological markers for hepatitis B virus infection in Australian Naval personnel.

In order to determine the prevalence of hepatitis B virus infection in Royal Australian Navy personnel and to formulate policies for their education, screening and vaccination, a voluntary survey was undertaken. Seven hundred and forty-eight subjects completed a questionnaire that provided details of age, sex, rank, ethnic origin, service abroad, length of service, history of tattooing, liver disease and blood transfusions. Serum was assayed by radioimmunoassay for the presence of hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (antiHBs) and antibody to hepatitis B core antigen (antiHBc). The presence of markers of hepatitis B virus infection was correlated with "risk factors" by means of the chi 2 test of independence. Fourteen (74%) of 19 personnel from the Pacific Islands, Asia and Africa who were excluded from analysis showed one-or-more such markers. The prevalence of any marker of hepatitis B virus infection was 4.4% (95% confidence interval [CI], 2.9%-5.9%). The individual markers HBsAg, antiHBs and antiHBc were found in 0.4% (95% CI, 0.1%-1.2%), 3.6% (95% CI, 2.2%-4.9%) and 3.9% (95% CI, 2.5%-5.3%) of subjects, respectively. The annual attack rate was estimated to be less than 1%. Factors which had a significant correlation with an increased prevalence of markers of hepatitis B virus infection included tattooing (especially if this had been performed in Asia), age, the duration of service and service abroad. Based on these data, and given the reduced cost of hepatitis B vaccines, vaccination now is considered worth while. A policy of vaccinating all personnel who may be required for service at sea, and others at risk, now is in effect. Educational programmes that are aimed at minimizing the risk of exposure to hepatitis B and other viral infections have been instituted.

Adolescent↗
PubMed1988

The effect of human recombinant macrophage colony-stimulating factor (CSF-1) on the murine mononuclear phagocyte system in vivo.

Human recombinant macrophage CSF (CSF-1) was administered i.v. to mice. After four daily injections there was a dose-dependent increase in the responsiveness of bone marrow cells from the treated animals to CSF-1 in vitro. At the highest dose tested (20,000 U/day) there was a selective 10-fold increase in the circulating population of mature monocytes. CSF-1 treatment also increased the macrophage content of the liver and peritoneal cavity and caused splenomegaly. The macrophages isolated from the peritoneum of CSF-1-treated animals were larger and expressed higher levels of the macrophage-specific F4/80 Ag. These data demonstrate that CSF-1 can act as a circulating regulator of the mononuclear phagocyte system.

Animals↗
PubMedDate not supplied

Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa.

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with 99mtechnetium (Tc)-stannous colloid (n = 13) or 111indium (In)-oxine (n = 10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [99mTc]-stannous colloid, while six [111In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease, activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4-9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.

Adolescent↗