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P Colp

Publications and source records attributed to P Colp.

7 recordsLinked to original sources
PubMed1997

Immunophenotyping of insulitis in control and essential fatty acid deficient mice treated with multiple low-dose streptozotocin.

Multiple injections of low-dose streptozotocin induce lymphocytic insulitis and autoimmune diabetes in male CD-1 mice. Prior to the onset of insulitis, macrophages infiltrate the islets (single cell insulitis) and presumably help initiate the lymphocytic response directed at streptozotocin-induced neoantigens on islet beta cells. Essential fatty acid deficiency ameliorates the lymphocytic insulitis and prevents diabetes in this model. We hypothesize that essential fatty acid deficiency, which perturbs eicosanoid pathways and blocks the production of inflammatory mediators such as leukotriene B4, might prevent or diminish the single cell insulitis and, thus, abrogate the lymphocytic response. The purpose of the study was to determine whether essential fatty acid deficiency causes any differences in the immunophenotype or the time course of single cell insulitis or insulitis after low-dose streptozotocin. Three to five essential fatty acid deficient and 3-5 control mice were treated with low-dose streptozotocin and killed on days 0, 3, 5, 8, 10, 12 and 15. Frozen sections of the pancreata were stained using an immunoperoxidase method with antibodies against mouse macrophages, CD4T-lymphocytes and CD8 T-lymphocytes. Sections were assessed for the presence and severity of single cell insulitis and insulitis. Based on cell counts in the most severely involved islet from each pancreas, there was no difference in the single cell insulitis in control and essential fatty acid deficient mice. Islets from control pancreata had a higher mean grade of lymphocytic insulitis. These findings suggest that autoimmune diabetes following low-dose streptozotocin in control mice is the result of both lymphocytic and histiocytic infiltrates with subsequent beta-cell destruction. Our results do not support the hypothesis that the protective effect of essential fatty acid deficiency is due to diminished influx of macrophages into the islets. It is, however, possible that essential fatty acid deficiency deleteriously affects macrophage function and, thus, blunts the lymphocytic response.

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PubMed1997

Immunophenotyping fish-to-mouse islet xenograft rejection: a time course study.

UNLABELLED: Tilapia islets, Brockmann bodies (BBs), transplanted under the kidney capsule (KC) of diabetic nude mice provide long-term normoglycemia, but, when transplanted into euthymic mice, reject in about one week. OBJECTIVES: The present study characterizes the cellular infiltrates at several time points during the xenograft rejection process. METHODS: Tilapia BBs were harvested, fragmented, cultured overnight, and then transplanted under the KC of streptozotocin-diabetic Balb/c mice. Glucose levels were measured daily until the mice were killed at 1 (n = 2), 2 (n = 2), 3 (n = 3), and 5 days (n = 3) post transplantation and at the time of BB graft rejection (n = 6). Serial frozen sections of graft-bearing kidneys were stained for murine macrophages (MOMA-2, F4/80, M170), CD4+ (L3T4) T-cells (YTS 191.1), and CD8+ (Ly-2) T-cells (YTS 169.4) by indirect immunoperoxidase; the presence of granulocytes and plasma cells was assessed with H&E stained sections. RESULTS: At 1 day, the grafts have undergone some central necrosis with macrophage infiltration. By 2 days, these changes are very well-developed and granulocytes, almost exclusively eosinophils, begin to surround the graft. At 3 days, rare CD4+ and CD8+ T-cells are seen at the graft kidney interface. Macrophages massively infiltrate the necrotic foci and pepper the graft. At 5 days and at rejection, macrophages and eosinophils predominated in the center of rejecting grafts while CD8+ T-cells and CD4+ T-cells were present at the periphery. Plasma cells were rare. CONCLUSION: We conclude that cell-mediated processes and eosinophils play roles in the rejection of cellular xenografts across this very wide phylogenetic barrier.

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PubMed1992

Comparative epidermal Langerhans cell migration studies in epidermal and epidermal/dermal equivalent grafts.

Immigration of Langerhans cell precursors from the peripheral blood to the skin was studied in human grafts placed on severe combined immunodeficient (SCID) mice. Monocyte fractions of human blood were injected intraperitoneally to SCID bearing either reconstituted (Langerhans cell free) epidermal sheets (E) or living skin equivalents (E/D) consisting of both epidermis and dermis. A range of immunocytochemical and ultrastructural markers was employed to monitor the colonization of the grafts, i.e., CD1a/c, Birbeck granules. In situ hybridization with probes against Alu sequences of human DNA were employed together with immunostaining for MHC class I mouse and human antigens to document graft survival. Although unequivocal LC were detected within E grafts, including both human (CD1a positive) and murine (NLDC-145 positive), no migration was achieved in the E/D situations.

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PubMed1991

Retardation in tumor growth and metastasis demonstrated in a human CLL B-cell line after the acquisition of an extra chromosome 11.

In this study we described the isolation of a subclonal EBV-transformed human CLL B-cell line with retarded growth rate and metastatic potential from its clonal parent (D10-1), which was karyotyped: 46.XY.dup(1)(q11----q32). The subclone, designated D10-1C, was isolated by limiting dilution of D10-1 following selection in 8-azaguanine-supplemented medium. Chromosome analysis of D10-1C revealed a constitution of 47,XY, + 11.dup(1)(q11----q32). This is the first demonstration that partial trisomy 1q-associated growth advantage in human cancer cells can be retarded by the presence of an additional dose of chromosome 11. Human chromosome 11 had been shown to be responsible for the suppression of tumor development. Whether the same suppressor genes are involved in D10-1C remains to be elucidated. The procedure described here for the enrichment and isolation of a growth-retarded mutant from D10-1 may be applicable in other malignant cell systems.

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PubMed1990

Role of 1q trisomy in tumorigenicity, growth, and metastasis of human leukemic B-cell clones in nude mice.

In order to investigate the association between various karyotypes of human tumor cells and biological behavior of tumors such as tumorigenicity, rate of growth, and the capacity to form metastasis, six chromosomally distinctive clones were isolated from an Epstein-Barr virus-transformed human chronic lymphocytic leukemic B-cell line which progressively grew and metastasized in irradiated nude mice. When inoculated into nude mice one clone (D10-1) with the karyotype of 46,XY,dup(1)(q11----q32) was more tumorigenic, grew faster, and produced more metastases than the other five clones. When mixtures of different clone-derived cells were grown in vitro or inoculated s.c. into nude mice the proportion of D10-1 cells was higher than their expected numbers in the cultures, s.c. tumors, and splenic and lymph nodal metastases. The growth and metastatic potential of the D10-1 clone were inhibited when cells from this clone were mixed with one or more clones that had slower growth. Duplication of 1q has been observed as a secondary aberration in human hematological malignancies and solid cancers. Our results demonstrate that duplication of the chromosome segment of 1q11----1q32 is associated with advantages in proliferation and metastasis formation.

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PubMedDate not supplied

Islet allograft rejection in rats: a time course study characterizing adhesion molecule expression, MHC expression, and infiltrate immunophenotypes.

Wistar Furth (RT1u) islets transplanted under the renal capsules of streptozotocin-diabetic Lewis (RT1l) rats reject after 5-6 days of normoglycemia. Hand-picked WF islets (1500-2000) were transplanted under the kidney capsules of diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B-cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells, parenchymal cells, and endothelial cells in five distinct compartments (i.e., peritoneal reflection, subcapsular perivascular space, islet grafts, graft-kidney interface, and kidney) were evaluated for expression of the various markers at each interval. Significant infiltrates arrived in three distinct waves in both iso- and allografts. First, macrophages blanketed the peritoneal capsular reflection and infiltrated by day 2. Second, the first wave of lymphocytes arrived in the edematous subcapsular soft tissue via capsular vessels by day 2 (allo > iso). Third, the second wave of lymphocytes arrived from the renal parenchyma to form a dense band at the graft-kidney interface and around grafts by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with CD4+ cells being mobilized first and from interstitial vessels throughout the entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in the infiltrates with the most intensely staining cells being intravascular. B-cells composed a very small proportion of infiltrating cells in both allo- and isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout. Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial cells, but neither was found on islet parenchymal cells. In conclusion, this study shows that islet allograft rejection is more complex than previously realized.

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