Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple myeloma (MM) is an incurable plasma cell cancer, localized in the bone marrow (BM). The mechanisms used by these cells to (re-)enter this organ remain largely unknown. Recently, we reported that both CD45+ and CD45- myeloma cells home to the BM and induce myeloma disease. In this work, we investigated the underlying mechanisms involved in the homing of CD45+ and CD45- myeloma cells in the experimental 5T2MM and 5T33MM murine models. In vivo tracing of flow cytometric sorted and radioactively labeled CD45 subsets revealed a reduced homing of the CD45- 5TMM cells to the BM as compared to the CD45+ 5TMM cells. Migration assays demonstrated an impaired chemotaxis towards BM endothelial cell conditioned medium, BM stromal cell conditioned medium and towards the basement membrane component laminin-1 of the CD45- 5TMM cells compared to the CD45+ subset. Matrix metalloproteinase-9 (MMP-9) and urokinase type plasminogen activator (uPA) are key extracellular matrix proteases involved in the invasion of cancer cells. Inhibitor and antibody blocking experiments demonstrated the involvement of both in the invasion of the 5TMM cells. CD45- 5TMM cells had a low secretion of MMP-9 and (for the non-aggressive line 5T2MM only) a low cell surface expression of uPA receptor, as revealed by gelatin zymography and flow cytometric analysis, respectively. Accordingly, the synthetic basement membrane invasive capacity of the CD45- 5TMM subpopulations was also impaired. Our results indicate that CD45+ and CD45- 5T myeloma cells have a differential BM homing attributable to differential migratory and invasive capacities.
 ...
PMID:Mechanisms involved in the differential bone marrow homing of CD45 subsets in 5T murine models of myeloma. 1249 87

Human processed lipoaspirate is a source of multipotent adult stem cells that are able to differentiate between mesenchymal and neurogenic lineage. We characterized PLA cells by cytometry and then they were cultured to induce differentiation into myogenic and neurogenic lineage. Lipoaspirates were digested with collagenase to obtain the pellet, which was labelled with anti-CD44, anti-CD45, and anti-CD90. We used BD FACS Calibur flow cytometer to acquire cellular events. Some cells were cultured at 37 degrees C and 5% CO(2) in neurogenic or myogenic medium and analysed by immunocytochemistry, using Neuron specific enolase, Vimentin, Glial fibrillary acidic protein, Tau, MAP2 to confirm neurogenic differentiation, MyoD1, Myosin heavy chain, Actin smooth muscle, vimentin to confirm myogenic differentiation. The cytometry results suggest that a part of the cells are of a mesenchymal origin, among which there are progenitor endothelial cells and leucocytes. Microscopy observation already reveals neuronal morphology and longitudinal multinucleated cells compared to control cells. Neurogenic cells only express NSE (early neuronal progenitor marker), but not GFAP, Tau, MAP2 (mature neuron and glial markers); myogenic cells are positive for MyoD1 and Myosin heavy chain. This demonstrates that lipoaspirate cells are capable of differentiating in vitro over a short period of time, and could be employed in biological and clinical research, like mesenchymal adult stem cells.
 ...
PMID:Characterization and induction of human pre-adipocytes. 1711 45

Ischemia of the heart, brain, and limbs is a leading cause of morbidity and mortality worldwide. Treatment with tissue type plasminogen activator (tPA) can dissolve blood clots and can ameliorate the clinical outcome in ischemic diseases. But the underlying mechanism by which tPA improves ischemic tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool and mobilizes CD45(+)CD11b(+) proangiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b(+) cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b(+) cells and VEGFR-1(+) cells, but not carrier-mobilized cells or CD11b(-) cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb ischemia. Thus, tPA mobilizes CD11b(+) cells from the BM and increases systemic and local (cellular) VEGF-A, which can locally promote angiogenesis during ischemic recovery. tPA might be useful to induce therapeutic revascularization in the growing field of regenerative medicine.
 ...
PMID:Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration. 2011 Apr 20

Patients with inflammatory bowel disease are susceptible to microvascular thrombosis and thromboembolism. The increased incidence of thrombosis is accompanied by enhanced coagulation and abnormalities in platelet function. Clinical studies have revealed thrombocytosis, alterations in platelet activation, enhanced platelet-leukocyte interactions, and elevated plasma levels of prothrombotic cytokines. This study was directed toward determining whether the thrombocytosis, altered platelet functions, and enhanced platelet-leukocyte interactions observed in patients with inflammatory bowel disease can be recapitulated in the dextran sodium sulfate and T-cell transfer models of murine colonic inflammation. Flow cytometry was used to characterize platelet function in heparin-anticoagulated whole blood of control mice and in mice with colonic inflammation. Platelets were identified by characteristic light scattering and membrane expression of CD41. Thiazole orange labeling was used to differentiate between immature and mature platelets. Platelet activation was monitored using the expression of an activation epitope of GPIIb/IIIa integrin. The combination of CD41, CD45.2, Gr-1, F4/80, and isotype control antibodies was used to detect and quantify aggregates of leukocytes, neutrophils, and monocytes with platelets. Our results indicated that colonic inflammation is associated with thrombocytosis, leukocytosis, and the appearance of immature platelets. An increased number of circulating activated platelets was detected in colitic mice, along with the formation of aggregates of leukocytes (PLA), neutrophils (PNA), and monocytes (PMA) with platelets. Selectin blockade with fucoidin inhibited dextran sodium sulfate-induced PLA formation. The findings of this study indicate that many features of the altered platelet function detected in human inflammatory bowel disease can be reproduced in animal models of colonic inflammation.
 ...
PMID:Platelet abnormalities during colonic inflammation. 2351 12