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PubMed1997

Patterns of graft infiltration and cytokine gene expression during the first 10 days of kidney transplantation.

Understanding of the events preceding acute cellular rejection of kidney transplants would be useful in the development of immunosuppressive strategies to prevent rejection. Information about these events in humans has been scarce, because of the lack of early, serial, biopsy samples. We took daily fine needle aspirates from kidney allografts for the first 10 days after transplant. Samples were analyzed by morphological cytology of graft-infiltrating cells, and reverse transcriptase-polymerase chain reaction for detection of interleukin (IL)-2, IL-4, IL-6, IL-10, and gamma-interferon gene expression. During the first 4 days, all of the grafts developed a low-grade monocyte-rich mononuclear cell infiltrate, accompanied by IL-10 gene expression. Thereafter, the infiltrates either remained stable or intensified. Of the 13 grafts with dense infiltrates, seven developed graft dysfunction. The remaining six did not, despite significant interstitial infiltrates. Both rejecting and nonrejecting dense infiltrates were associated with a biphasic pattern of IL-2 and gamma-interferon gene expression, preceding and accompanying lymphocytic graft infiltration. Grafts that did not develop dense infiltrates had no detectable IL-2 or gamma-interferon gene expression and did not suffer cellular rejection during the study period. The development of both rejecting and nonrejecting infiltrates was strongly associated with DR mismatches between donor and recipient. IL-2 and gamma-interferon gene expression are necessary, but not sufficient, for the development of acute cellular rejection in the first 10 days of kidney transplantation, and are more closely associated with the period leading up to rejection than with the period of graft dysfunction.

Acute Disease↗

PubMed1994

Immunohistological study of the development of the cellular infiltrate in the pelage follicles of the DEBR model for alopecia areata.

The Dundee experimental bald rat (DEBR) undergoes hair loss associated with perifollicular infiltrates of mononuclear cells (MNC), a pathological characteristic of human alopecia areata (AA). To investigate further the pathogenesis of the disease in this animal model, we have studied the development, composition and extent of the perifollicular MNC infiltration in young (6-week-old), prelesional (3-month-old), active lesional, and established lesional DEBR rats, using 6-week- and 6-month-old Wistar rats as normal controls. The proportions of hair follicles showing infiltration by MNC and their main subsets were determined using immunohistochemical staining of serial cryostat sections of flank skin biopsies. There was a good correlation between the degree of leucocyte (OX-1+) infiltration of anagen hair follicles and the development of hair loss. In 6-week-old DEBR skin, there were few perifollicular cells expressing MHC class II, with positively stained dendritic cells in the dermis above the sebaceous gland. There was a sparse perifollicular distribution of CD4+ cells (W3/25) and macrophages (ED-1+). No CD8+ cells (OX-8+) were seen associated with DEBR hair follicles, and only small numbers were present in Wistar rats. In prelesional DEBR rats there was an increased perifollicular presence of MHC class II+ cells, macrophages, and particularly of CD8+ cells, with little change in CD4+ cells. Active and established lesional rats, i.e. animals with overt loss of hair, showed a significant increase in the degree of MNC infiltration and the proportion of infiltrated follicles, the majority of which were in dystrophic anagen. In the perifollicular infiltrate the CD4+:CD8+ ratio was approximately 2:1. An intrafollicular infiltrate was prominent, and was composed of CD8+ cells and macrophages, with bulbar and suprabulbar keratinocytes expressing MHC class II antigens. CD4+ cells were not detected in follicular epithelium. ICAM-1 expression correlated with MNC infiltration. These results show marked similarities to lesional human AA. They also focus on a possible active role for CD8+ cells in the pathogenesis of hair loss in the DEBR rat.

Alopecia Areata↗

PubMed2006

Pulpal anaesthesia for mandibular permanent first molar teeth: a double-blind randomized cross-over trial comparing buccal and buccal plus lingual infiltration injections in volunteers.

AIM: To compare the efficacy of buccal and buccal plus lingual infiltration anaesthesia for permanent mandibular first molars. METHODOLOGY: Thirty one healthy adult volunteers received each of the following methods of anaesthesia for a mandibular first molar tooth in a randomised order, 1) Buccal infiltration of 1.8 mL and needle penetration lingually. 2) Buccal infiltration of 0.9 mL, plus lingual infiltration of 0.9 mL. Two percent lidocaine with 1:100,000 epinephrine was used. Electrical pulp testing was performed before, and every 2 minutes for 30 minutes after injection. A successful outcome was recorded as the absence of pulp sensation on two or more consecutive maximal pulp tester stimulations (80 microA). Injection discomfort was assessed using visual analogue scales. Data were compared with McNemar and Wilcoxon Signed Ranks tests. RESULTS: Buccal infiltration was successful in 38.7% of cases compared to 32.3% after combined infiltrations; the difference was not significant (P = 0.63). Buccal infiltration produced more episodes of no response to maximum stimulation than buccal and lingual infiltrations (129 and 114 respectively), this difference was not significant (P = 0.11). Peak anaesthetic effect occurred around 10-14 minutes after injection. There was no difference in injection discomfort between buccal injections of 0.9 mL and 1.8 mL of solution (P = 0.90). Lingual injection was more uncomfortable than lingual penetration (P = O.O02). CONCLUSIONS: Buccal and buccal plus lingual infiltrations did not differ in their efficacy in producing anaesthesia of permanent first molar teeth.

Adult↗

PubMed2001

Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis.

OBJECTIVE: Eosinophils infiltrate the colonic mucosa of patients with collagenous colitis (CC), although the pathogenetic implications are unknown, including whether these eosinophils are activated and degranulate in situ. We examined eosinophil infiltration and degranulation in the intestines of patients with CC by immunofluorescence for eosinophil granule major basic protein (MBP). METHODS: We used both conventional histology (hematoxylin and eosin) and indirect MBP immunofluorescence histochemistry on colon biopsy specimens from patients with CC (n = 21) and from healthy controls (n = 9). Scoring of histological features was performed on hematoxylin and eosin-stained sections on a 0 to 3 scale. Eosinophil infiltration and degranulation, as quantified by extracellular MBP staining, were scored in each specimen on a 0 to 4 scale. RESULTS: The inflammatory infiltrate of the lamina propria, the thickness of the collagen band, the numbers of intraepithelial lymphocytes, and degree of epithelial cell damage were all significantly increased in patients with CC as compared to controls (p < 0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p < 0.0001). The degree of infiltrating eosinophils by hematoxylin and eosin was correlated with eosinophil infiltration and degranulation by MBP immunostaining; however, no other correlations were found between eosinophil infiltration or degranulation by immunofluorescence and any of the histological parameters measured in the CC group. CONCLUSIONS: Eosinophil infiltration and degranulation are increased in the colonic mucosa of patients with CC compared to healthy controls. Eosinophils and their cytotoxic granule proteins could be involved in the pathogenesis of CC. Further studies will be necessary to elucidate the mechanisms of eosinophil activation in CC.

Adult↗

PubMed1980

Gonadal infiltration in children with leukaemia and lymphoma.

In a postmortem survey of children with leukaemia and lymphoma, the overall incidence of testicular infiltration was 65% and of ovarian infiltration 66%. In acute lymphoblastic leukaemia, testicular infiltration was found in 25 of 39 cases and ovarian infiltration in 6 of 12 cases. The majority of boys with acute lymphoblastic leukaemia and testicular infiltration also had infiltration in other organs; furthermore, in most cases without testicular infiltration leukaemic infiltration was found in other organs. The findings of this survey support the view that testicular infiltration is indicative of widespread disease.

Acute Disease↗

PubMed2004

Depletion of tumor-infiltrating macrophages is associated with amphoterin expression in colon cancer.

Macrophage infiltration into colon cancer and amphoterin expression in cancer cells was examined in 42 human colon cancers invading the subserosa. The mean number of infiltrating macrophages was significantly higher in Dukes' B cases than in Dukes' C cases (p = 0.0065). Tumors with few infiltrating macrophages (macrophage depletion) were significantly more frequent in Dukes' C cases than in Dukes' B cases (p = 0.0014). No Dukes' C cases with relevant macrophage infiltration showed macrophage-cancer cell contact, whereas 5 Dukes' B cases showed such contact (p < 0.0001). In human colon cancer cells implanted in the cecum of nude mice, KM12SM (highly metastatic) tumors yielded less macrophage infiltration and more liver metastases than KM12C (low risk of metastasis) tumors (14 +/- 3 vs. 78 +/- 32 and 24 +/- 6 vs. 5 +/- 3 per liver, respectively). Amphoterin expression was detected at high frequency in both Dukes' B and C cases (p = 0.0684). In macrophage-depleted cases, amphoterin expression was significantly higher than that in non-depleted cases (p = 0.0015). To confirm biological effects of amphoterin on macrophages, an infiltration assay using the cell-layered Boyden chamber was done. Infiltration of PMA-treated U937 monocytes through the KM12SM cell layer was increased by pretreatment of KM12SM cells with amphoterin antisense S-oligodeoxynucleotide exposure. Moreover, extracted amphoterin inhibited PMA-U937 monocyte infiltration in a dose-dependent manner. Thus, amphoterin may play an important role in the inhibition of macrophage infiltration into colon cancer.

Adenocarcinoma↗

PubMed1987

Immunohistochemical study of mononuclear cell infiltrates in squamous cell carcinoma of oral cavity and paranasal sinus.

Serial frozen sections were prepared from 22 squamous cell carcinomas of oral cavity and paranasal sinus. Mononuclear cell infiltrates were stained by the biotin-avidin-horseradish peroxidase method using a panel of 10 mouse monoclonal antibodies to human leukocyte antigens. The degree of infiltration was graded from + + + (marked) to - (absent). The infiltration of anti-Leu-4-reactive cells (Leu-4+ cells) was grade + + or + + + in 14 of 22 cases. In 13 of 22 cases, infiltration of Leu-3a + 3b+ cells (helper/inducer T lymphocytes) was grade + + (moderate). In 5 of 20 cases, infiltration of Leu-2a+ cells (cytotoxic/suppressor T lymphocytes) was grade + +. As for B lymphocytes, infiltration of Leu-12+ cells was grade + + in only 2 of 19 cases. In conclusion, T lymphocyte infiltrates were commonly seen in squamous cell carcinoma in oral cavity and paranasal sinus and the number of patients with grade + + infiltration of helper/inducer T lymphocytes significantly predominated over that of patients with infiltration of cytotoxic/suppressor T lymphocytes grade + +.

Adult↗

PubMed2004

Reassessment of diagnostic criteria in cutaneous lymphocytic infiltrates.

CONTEXT: Non-specific lymphocytic infiltrates of the skin pose difficulties in daily practice in pathology. There is still a lack of pathognomonic signs for the differential diagnosis between benign and malignant lymphocytic infiltrates. OBJECTIVE: To evaluate the morphological and immunohistochemical profile of lymphocytic infiltrations of the skin according to clinical outcome. TYPE OF STUDY: Retrospective; histopathological and immunohistochemical analysis. SETTING: Referral center, university hospital. SAMPLE: 28 cases of lymphocytic infiltrates of difficult differential diagnosis selected from the records. MAIN MEASUREMENTS: Eighteen histological variables and the immunophenotypic profile were assessed using the CD4, CD8, CD3, CD20 and CD30 lymphoid markers and compared to subsequent follow-up. RESULTS: The most common diagnoses were: initial mycosis fungoides (eight cases) and drug reactions (five cases). Single morphological variables did not discriminate between benign and malignant infiltrates except for the presence of Pautrier-Darier's microabscesses, which were found only in mycosis fungoides (p = 0.015). Patterns of superficial and deep infiltration (p = 0.037) and also the presence of eosinophils (p = 0.0207) were more frequently found in benign lymphocytic infiltrates. Immunohistochemical profile of T-cell subsets showed overlap between benign and malignant infiltrates with a predominance of CD4-positive (helper) lymphocytes in the majority of cases. CONCLUSIONS: A combination of clinical and histological features remains the most reliable approach for establishing a definite diagnosis in cases of lymphoid skin infiltrates.

Antigens, CD↗

PubMed1999

Complete percutaneous excision of infiltrating carcinoma at stereotactic breast biopsy: how can tumor size be assessed?

OBJECTIVE: The purpose of this study was to determine the frequency of complete excision of infiltrating carcinoma at stereotactic 11-gauge directional vacuum-assisted breast biopsy and to evaluate the feasibility of measuring tumor size in stereotactic biopsy specimens in infiltrating carcinomas that were percutaneously excised. MATERIALS AND METHODS: We performed retrospective review of 51 infiltrating carcinomas diagnosed using stereotactic 11-gauge directional vacuum-assisted biopsy that underwent subsequent surgery. For lesions yielding no residual infiltrating carcinoma at surgery, the maximal dimension of the tumor was measured in stereotactic biopsy specimens using ocular micrometry. RESULTS: In 10 (20%) (95% confidence intervals, 9.8-33.1%) of 51 infiltrating carcinomas diagnosed at stereotactic biopsy, surgery revealed no residual infiltrating carcinoma. Complete excision of infiltrating carcinoma was more frequent if 14 or more specimens were obtained (32% versus 0%, p < .004), if the mammographic lesion was removed (35% versus 7%, p < .03), and if the mammographic lesion size measured 0.7 cm or less (50% versus 16%, p = .08). Tumor size in stereotactic biopsy specimens was within 3 mm of mammographic lesion size in six (60%) of 10 lesions, including five (71%) of seven masses and one (33%) of three calcification lesions, but was smaller than the mammographic lesion size in eight (80%) of 10 lesions. CONCLUSION: Surgery revealed no residual infiltrating carcinoma in 10 (20%) of 51 infiltrating carcinomas diagnosed at stereotactic 11-gauge biopsy. Although tumor size can be assessed in stereotactic biopsy specimens in these lesions, such measurements may underestimate the maximal dimension of the tumor. Further study is needed to evaluate the usefulness of these measurements in guiding treatment decisions.

Adult↗

PubMed2000

[Dendritic cell infiltration in lung adenocarcinoma and its effect on prognosis].

OBJECTIVE: To study the infiltration degree of dendritic cells in lung adenocarcinoma and its effect on prognosis. METHODS: S-100 protein was used as the specific marker for dendritic cells, and immunohistochemistry was employed to detect the distribution of dendritic cells in lung adenocarcinoma. RESULTS: Among 46 cases of lung adenocarcinoma, 19 were markedly infiltrated by dendritic cells, the five-year survival rate being 61%; 27 showed slight infiltration, the five-year survival rate being 21%. Among the 46 cases of adenocarcinoma, 26 were low differentiated adenocarcinoma, in which 10 were infiltrated markedly by dendritic cells, five-year survival rate being 57%; and 16 were slightly infiltrated, five-year survival rate being 16%. These data were evaluated with the log-rank test, which showed a significant difference between the markedly infiltrated group and the slightly infiltrated group. CONCLUSION: The prognosis of lung adenocarcinoma which markedly infiltrated by dendritic cells is better than that of slightly infiltrated by dendritic cells.

Adenocarcinoma↗

PubMed2002

Digital image analysis system for the quantification of infiltrates and cell adhesion molecules in inflammatory cardiomyopathy.

BACKGROUND: We attempted to develop a digital image analysis (DIA) system for endomyocardial biopsies (EMBs) to reliably quantify a) biopsy quality, b) immunohistochemically-marked infiltrates, and c) cell adhesion molecules (CAMs) in relation to net heart area (HA) for the semi-automated diagnosis of inflammatory cardiomyopathy (InfCM). MATERIAL/METHODS: 140 EMBs from dilated cardiomyopathy (DCM) patients and 14 autopsy heart samples (controls) were immunostained for T-lymphocytes (CD2, CD3, CD4, CD8), beta(2)-integrin+ infiltrates (CD18, LFA-1, Mac-1) and CAMs (immunoglobulin superfamily: ICAM-1, HLA class I, HLA DR, VCAM-1, CD58; selectins: CD62E and CD62P; and the beta(1)-integrin chain CD29). EMB quality was assessed visually on a three-point scale. Infiltrates were quantified visually (per hpf) and by DIA (per mm2 HA). CAM expression was evaluated semiquantitatively and by DIA (area fraction [AF]: stained area relative to HA). RESULTS: DIA-evaluated HA correlated significantly with the visual assessment of EMB quality. The visual evaluation of both infiltrates and CAMs correlated significantly with the respective DIA-based quantification. DIA-quantified CAM-AF and infiltrates were discriminated by the CAM classification (CAMs+: n=87; 62%) compared to controls. DIA-quantified CAM immunoreactivity correlated significantly with the DIA-quantified counter-receptor+ infiltrates. DIA evaluation of biopsy quality, infiltrates, and CAMs was devoid of inter- and intraobserver variability. CONCLUSIONS: The DIA system presented here enables standardized and observer-independent assessment of EMB quality and intramyocardial inflammation (density of infiltrates and CAM expression) in DCM biopsies related to HA. Our data confirm that endothelial CAM count and counter-receptor+ immunocompetent infiltration are interdependent pathogenic and diagnostic hallmarks of InfCM.

Adult↗

PubMed1990

Tumor-infiltrating lymphocytes from human colon carcinomas. Functional and phenotypic characteristics after long-term culture in recombinant interleukin 2.

Tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes from 7 patients with adenocarcinoma of the colon were evaluated for expansion and antitumor activities during culture in the presence of 1000 U/ml of recombinant human interleukin 2. Functional and phenotypic characteristics of tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes were compared between weeks 2 and 3 of culture in recombinant interleukin 2. All but one tumor-infiltrating lymphocyte and all autologous peripheral blood lymphocyte preparations proliferated well in vitro. Tumor-infiltrating lymphocytes expanded better (p less than 0.05) than autologous peripheral blood lymphocytes, reaching median-fold expansions of 2231 (range 1-4720) and 108 (range 13-1263), respectively. Cytotoxicity of interleukin 2-activated tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes against fresh autologous or allogeneic colon carcinoma targets was relatively low in these cultures. Due to better proliferation, tumor-infiltrating lymphocytes showed significantly greater (p less than 0.05) total cytotoxic activity per culture against fresh autologous tumor-cell targets than did autologous peripheral blood lymphocytes, achieving a median total lytic units of activity per culture of 671 compared with 92 for autologous peripheral blood lymphocytes. Cytotoxicity was not restricted to autologous tumor cells. Two-color flow cytometry demonstrated that the predominant proliferating cell population in interleukin 2-expanded long-term cultures of tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes expressed the CD3+Leu19- phenotype. Some cultures were enriched in CD3+ Leu19+ and CD3-Leu19+ cells. This study indicated that tumor-infiltrating lymphocytes from most but not all human primary colon adenocarcinomas could be expanded in the presence of recombinant interleukin 2 and mediate non-major histocompatibility complex-restricted antitumor cytotoxicity. Because fresh colon carcinoma cells appear to be resistant to in vitro lysis by interleukin 2-activated tumor-infiltrating lymphocyte and autologous peripheral blood lymphocyte effectors, the role of adoptive immuno-therapy in treatment of advanced colon carcinomas in humans may have to be reevaluated.

Adenocarcinoma↗

PubMed1977

Lymphocytic infiltration in choroidal melanoma and its prognostic significance.

Lymphocytic and plasmacytic infiltration surrounding a malignant tumour probably represents an immunological response of the host directed against the neoplasm. Lymphocytic infiltration has a favourable effect on the prognosis in a number of human tunours, including cutaneous melanoma. The present study includes 326 consecutive cases of cholroidal melanoma which were examined for cellular infiltration. These data were then correlated with other histological parameters and with prognosis. An intense cellular infiltration was found in fifteen tumours (4.6 per cent) and a moderate infiltration in forty (12.3 per cent). Tumours with cellular infiltration were significantly larger and more vascularized than the remaining tumours, which may relate to the accessibility of the immune system to the tumour. There was a higher percentage of poorly differentiated tumours among those with cellular infiltration. However, it does not appear that cellular infiltration favourably influences the prognosis of choroidal melanoma, as 5-year survival rates did not correlate with the degree of cellular infiltration demonstrated by the primary tumour. Although choroidal melanomas are capable of inciting an immune response, this response is apparently ineffective in preventing metastastic spread.

Choroid Neoplasms↗

PubMedDate not supplied

Effect of long-term diet enrichment with selenium, vitamin E and vitamin B15 on the degree of fatty infiltration of the liver.

In a two-year experiment on 190 Wistar rats the effects were studied of the aging process and diet enrichment with selenium, vitamin E and vitamin B15 (pangamic acid) on the degree of fatty infiltration of the liver determined histochemically with Oil Red O. The degree of fatty infiltration of the liver was assessed by the method of quantitative analysis using a computer image analyser Quantimet 720. System 30 (Cambridge Instruments). The process of aging of the animals was associated with increasing fatty infiltration of the liver. Selenium had a two-phase effect on the degree of fatty infiltration: in the first 12 months of selenium administration (0.1 ppm of sodium selenite per 100 g of the diet) fatty infiltration of the liver was decreasing, and after 18 months of the experiment this effect disappeared and the degree of fatty infiltration was not different from that in the control group. Contrary to this, vitamin E administration 6 mg/100 g of the diet increased the degree of fatty infiltration during the first 12 months. After 18 months a reverse effect appeared with inhibition of the progression of fatty infiltration. Thus the two-phase effect of vitamin E was a reverse of selenium effect. Addition of vitamin B15 to the diet (2.5 mg/100 g of diet) increased the degree of fatty infiltration of the liver which was maintained at a stable level throughout the whole experiment, i.e. 12-18 months.

Animals↗

PubMed1981

[Studies on parametrial infiltration of uterine cervical cancer (author's transl)].

It is clear that the prognosis of uterine cervical cancer depends on the spread of cancer, especially lymphnodes metastases and parametrial infiltration. The correct diagnosis of parametrial infiltration before treatment is, however, difficult and there are many over- and under-diagnosis. In this paper, we discuss the details of parametrial infiltration based on the radically hysterectomized specimens in Shinshu University Hospital from 1964 to 1978. In these period, 284 cases of uterine cervical cancer were operated by Okabayashi's radical hysterectomy and our postoperative classification were carried out. The results were as follows; 1) The incidence of parametrial infiltration were 16.4 in Stage Ib, 36.6% in Stage IIa, 57.5% in Stage IIb and 35.6% in all cases. 2) When divided the parametrial tissue into three parts, we could find carcinomatous infiltration into uterine part in 77.3% of positive cases, middle part in 16.2% and pelvic part in 16.2%. 3) The agreement between clinical diagnosis and histological findings were 72.2% in all cases. 4) The CPL classification had close relation with parametrial infiltration (C type; 0%, P type; 17.9%, L type; 61.8%). 5) The 5-year survival rate of patients with infiltration showed poor outcome (63.0% in 81 cases), but that with no infiltration had good prognosis (98.4% in 128 cases). In conclusion, parametrial infiltration is very important for treating the uterine cervical cancer patients.

Adnexa Uteri↗

PubMed1995

Nerve root infiltration and sympathetic block. An experimental study of intraradicular blood flow.

STUDY DESIGN: The nerve root of L7 was exposed, and a clamp was applied to simulate radiculopathy. Intraradicular blood flow was measured at the takeoff point of the nerve root and at the distal to the dorsal root ganglion before and after nerve root infiltration with 2% lidocaine or physiological saline solution (control group), or sympathetic ganglion block with 2% lidocaine. OBJECTIVES: To investigate one of the mechanisms of the therapeutic effect of nerve root infiltration by assessing changes in intraradicular blood flow. SUMMARY OF BACKGROUND DATA: Increased intraradicular blood flow was noted both proximal and distal to the clamp after nerve root infiltration or sympathetic ganglion block with 2% lidocaine. No increase was seen after nerve root infiltration with saline solution. Macroscopic and microscopic examination showed that dye after nerve root infiltration did not spread beyond the clamped region to the proximal site. METHODS: Intraradicular blood flow was measured with a tissue blood flowmeter using the electrolytic hydrogen clearance method before and after nerve root infiltration with 2% lidocaine or physiologic saline solution (control group), or sympathetic ganglion block with 2% lidocaine. RESULTS: Increased intraradicular blood flow was noted both proximal and distal to the clamp after nerve root infiltration or sympathetic ganglion block with 2% lidocaine. No increase was seen after nerve root infiltration with saline solution. CONCLUSIONS: An increase in intraradicular blood flow is related to one of the mechanisms of the therapeutic effect of nerve root infiltration. This effect may be mediated by the sympathetic nervous system.

Animals↗

PubMed1995

Phenotypic analysis of the glomerular and periglomerular mononuclear cell infiltrates in the Thy 1.1 model of glomerulonephritis.

BACKGROUND: The phenotype of macrophages invading the mesangium and periglomerular region has not been described in experimental mesangial proliferative glomerulonephritis, although it has implications for the mechanism of entry of these cells into these locations and their function once there. We have, therefore, determined the phenotype of the periglomerular leukocytic infiltrate in the Thy 1.1 model of mesangial proliferative glomerulonephritis and compared it with that of cells invading the mesangium. EXPERIMENTAL DESIGN: The Thy 1.1 model was induced in Lewis rats, and sections were taken at 1 hour and at 1, 4, 9, 30, and 90 days postinduction. Immunohistochemistry was performed using monoclonal antibodies against macrophage markers (ED-1, CD4, RT1-B, and ED-2), chains of the beta 2 integrins (CD18, CD11a, and CD11b), T and B cell markers (CD8, T cell receptor, interleukin-2 receptor, and MRC OX33), and markers of mesangial cell proliferation (proliferating cell nuclear antigen, alpha-smooth muscle actin). Sections were compared with those obtained from control animals. RESULTS: In untreated rats, a striking resident periglomerular macrophage population (phenotype ED-1-ve ED-2-ve CD4+ve RT1-B+ve CD18+ve CD11a+ve CD11b+ve) was found, confirming a previous report. From 24 hours postinduction, this resident macrophage population was supplemented by a population whose predominant phenotype (ED-1+ve ED-2-ve CD4+ve RT1-B+ve CD18+ve CD11a+ve CD11b+ve) was identical to that of macrophages infiltrating the mesangium. Both infiltrates peaked at 4 days and returned to base-line levels by 1 to 3 months. There was no significant lymphocyte infiltrate within the glomerulus and only a minimal periglomerular T cell infiltrate. CONCLUSIONS: These data show, first, that disease limited to the mesangium can lead directly to periglomerular macrophage infiltration. Second, the presence of CR3 (i.e., CD11b and CD18) and LFA-1 (i.e., CD11a and CD18) on the macrophage infiltrate indicates that both ligands are important for cells to enter the mesangium and periglomerular areas. Third, the marked phenotypic and temporal similarities between the mesangial and periglomerular macrophage infiltrates suggests that a common factor(s) is involved in their pathogenesis. Finally, expression of RT1-B (Ia) but not ED-2 is reported to be typical of interstitial dendritic cells rather than tissue macrophages, suggesting a unique function for the glomerular and periglomerular macrophage infiltrate in this model.

Animals↗

PubMed1994

Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice.

The nonobese diabetic mouse is a relevant model for insulin-dependent diabetes mellitus which results from the destruction of pancreatic beta cells by mononuclear cells infiltrating the islets of Langerhans. Other organs such as salivary glands display inflammatory infiltration. Using immunohistochemical and flow cytometry analyses, we have studied the expression of diverse homing and adhesion molecules in salivary glands and the pancreas in nonobese diabetic mice. In salivary glands, ICAM-1 was expressed by endothelial and dendritic cells within the lymphocytic infiltration. HEV-like structures expressing PNAd were observed in the areas of lymphocytic infiltration whereas MAdCAM-1 was absent. Lymphocytes infiltrating salivary glands expressed LFA-1 and Pgp-1 although Mel-14 Ag was absent. In infiltrated islets, ICAM-1 was expressed by endothelial cells, dendritic cells, and mononuclear cells. We confirm the presence of HEV-like structures expressing MAdCAM-1 and PNAd in inflamed islets. With regard to peripheral lymphocytes, the proportion of CD4 and CD8 cells expressing Mel-14 was decreased in the infiltrated islets, whereas the expression of LFA-1, Pgp-1, and LPAM-1/2 was increased. B lymphocytes exhibited up-regulation of LPAM-1/2. Moreover, the proportion of CD4, CD8, and B lymphocytes expressing CD69 was increased in the pancreas. These results indicate that first, infiltration of islets of Langerhans results at least partly from modifications of adhesion molecule expression in the pancreas, which allow extravasation of mononuclear cells into the islets via at least three different pathways; and second, that activated cells are concentrated in the infiltrates as compared with peripheral lymphoid organs.

Animals↗