Search PubMed⌕ Search

Biomedical subjects

A J Coito

Publications and source records attributed to A J Coito.

28 records · Page 2Linked to original sources
PubMed1994

The expression of extracellular matrix proteins during accelerated rejection of cardiac allografts in sensitized rats.

Extracellular matrix (ECM) proteins exert comitogenic effects on T cell activation in vitro, and may play a role in selective lymphocyte migration and tissue positioning in vivo. However, putative roles of ECM in host immune responses leading to graft rejection remain largely obscure. The present study evaluates intragraft expression of prominent ECM components, laminin (LN) and fibronectin (FN), and analyzes their interactions with host cellular repertoire in a well-defined cardiac allograft model in sensitized rats. (LEW x BN)F1 cardiac allografts are rejected within 24 hr in sensitized LEW rats. Immunohistochemical analysis has revealed that this brisk rejection response was associated with an early increase in the intermyocyte and endothelial deposition of LN and FN at the graft site, with their peak at 6 hr after transplantation. The upregulation of ECM preceded intragraft cellular infiltration, which at 6 hr consisted primarily of monocytes and macrophages. The infiltrating cells localized selectively in FN-rich cardiac interstitial and perivascular areas, as documented by two-color staining and laser scanning confocal microscopy. Marginal and transient increase in ECM expression was noted within control isografts. Next, we tested the role of ECM proteins in systemic lymphocyte recirculation. Specifically sensitized lymph node lymphocytes (LNL) were labelled in vitro with a DNA-binding fluorochrome, H33342, and injected i.v. into secondary engrafted recipients, which were sacrificed 6 hr later. These LNL were detected within host cervical lymph nodes in close association with FN deposits. Moreover, LNL labeled in vitro with a cationic membrane-binding fluorochrome, Di "I", were traced in hosts the lymph nodes of which were analyzed for simultaneous detection of LN and FN. Again, transferred LNL migrated selectively to FN-containing compartments, as shown by laser scanning confocal microscopy. Thus, ECM proteins should be regarded as active and important participants in host immune responses leading to graft rejection. FN may act as an ECM component "signal" for graft-infiltrating cells, and may play a key role in selective homing and specific tissue positioning of recirculating specifically sensitized lymphocytes in host peripheral lymphoid tissues.

Animals↗
PubMed1994

The role of cellular and extracellular matrix adhesion proteins in organ transplantation.

The specific adhesion of cells to other cells or to particular tissue microenvironments is a basic function of cell migration and recognition, and underlines many biologic processes including embryogenesis, repair and immunity. Leukocytes express an array of surface receptors broadly known as "accessory adhesion molecules." which mediate most cell-cell interactions, direct lymphocyte traffic between anatomical compartments, and facilitate cellular adhesion to the inflammation or alloantigenic sites (Springer 1990). In addition, adhesion molecules are involved in the process of antigen recognition, and may costimulate cell activation and transformation. These proteins are thought to affect the very early antigen independent events between host leukocytes and vascular endothelium. Because of these activities, the subject of adhesion molecules is gaining interest in the field of organ transplantation, in both conceptualization and development of novel therapeutic strategies (de Sousa et al. 1991, Kupiec-Weglinski et al. 1993a, Heemann et al. 1993).

Animals↗
PubMedDate not supplied

Fibronectin-alpha4beta1 integrin interactions modulate p42/44 MAPK phosphorylation in steatotic liver cold ischemia-reperfusion injury.

We investigated the effects of the connecting segment-1 (CS1) peptide, which blocks fibronectin (FN)-alpha4beta1 integrin interactions upon cell signaling, leukocyte migration, and secretion of proinflammatory cytokines, in a well-established steatotic rat liver model using ex vivo cold ischemia followed by isotransplantation. In this model, CS1 peptides were administered through the portal vein of steatotic Zucker rat livers prior and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplantation (OLT) received an additional 3-day course of CS1 peptides post-OLT. CS1 peptide-treated steatotic OLTs harvested at 1, 3, and 7 days showed moderated levels of p42/44 mitogen-activated protein kinase (MAPK) phosphorylation, comparable to those observed in steatotic naive livers. In contrast, p42/44 MAPK phosphorylation was found up-regulated in 1- to 3-day damaged control OLTs. However, 7-day control OLTs were characterized by virtually lack of p42/44 MAPK phosphorylation. Lack of p42/44 MAPK phosphorylation in 7-day control OLTs was correlated with massive presence of leukocytes in the grafts and elevated levels of proinflammatory cytokines. CS1 peptide-treated OLTs at 7 days showed a profound decrease in T-cell (10 +/- 3 vs 56 +/- 20, P < .03) and monocyte/macrophage (+/++ vs +++) infiltration and significantly reduced levels of cytokine expression, such as IL-2 (approximately sixfold), and IFN-gamma (approximately three- to fourfold), as compared with controls.

Animals↗
PubMedDate not supplied

Adhesion molecule interaction with extracellular matrix.

The role of extracellular matrix (ECM) proteins in supporting tissue structure and modulating cell moltility or phagocytosis is well established. Recent demonstration of complex in vitro interactions between lymphocytes and ECM components mediated by an array of cell surface adhesion receptors supports the role ECM may play in physiological functioning of the immune system in vivo, e.g. cell activation, migration and positioning in specific tissue microenvironments. Thus, ECM components and their lymphocyte adhesion ligands should be considered as active participants in the host immune responses, including that triggered by transplantation of an MHC-incompatible organ graft.

Animals↗