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

Strategies directed against activated neutrophils have reduced ischemia-induced brain injury. However, therapies targeted specially against the neutrophil adhesion protein L-selectin have not yet been examined in stroke. This study therefore examined the effects of a monoclonal antibody directed against L-selectin in a rabbit model of thromboembolic stroke with (n = 16) or without (n = 10) concomitant t-PA therapy. Rabbits received either the humanized monoclonal antibody DREG200 directed against the L-selectin receptor or humanized control monoclonal antibody HuDREG55 which does not bind to rabbit L-selectin in addition to t-PA therapy (n = 8, each group). HuDREG200 (2 mg kg-1 i.v.) was given as a bolus 3 h following clot embolization, followed immediately by a 2 h intravenous infusion of t-PA (6.3 mg kg-1. Without t-PA therapy rabbits received HuDREG200 (2 mgkg-1, i.v.; n = 5) or HuDREG55 (n = 5) 1 h following clot embolization. The group receiving HuDREG200 in addition to t-PA demonstrated a moderate improvement in brain infarct size (8.4 +/- 2.4 vs. 13.5 +/- 3.5, %hemisphere, mean +/- sem), ICP (final reading 10.0 +/- 1.6 vs. 12.4 +/- 3.0 torr) and restoration in regional cerebral blood flow (30.2 +/- 7.8 vs. 21.6 +/- 10.9 cc 100 g-1 min-1) when compared to t-PA therapy alone although statistical significance was not achieved. No efficacy was demonstrated in the group receiving HUDREG200 without concomitant t-PA therapy. The results suggest the addition of a humanized anti-L-selectin monoclonal antibody HuDREG200 in combination with t-PA may further improve outcome in acute thromboembolic stroke, although future studies are necessary to support these findings.
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PMID:Humanized anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke. 966 85

Effective cell-mediated antitumor immunity requires the activation of tumor-reactive T cells and the trafficking of activated T cells to tumor sites. These processes involve the extravasation of lymphocytes from the blood and lymphatics, and their homing to lymph nodes and tumors. L-selectin (CD62L) is an important molecule in these processes. It directs naive lymphocytes to peripheral lymph nodes where they become activated and it traffics naive lymphocytes to inflammatory environments, such as tumors. Individuals with advanced cancer are immune suppressed due to myeloid-derived suppressor cells (MDSC), a population of immature myeloid cells that accumulate to high levels in response to tumor-secreted and proinflammatory factors. We now demonstrate that the reduction in T cell levels of L-selectin that is commonly seen in individuals with cancer inversely correlates with MDSC levels. Three lines of evidence demonstrate that MDSC directly down-regulate L-selectin on naive T cells: 1) naive T cells cocultured with tumor-induced MDSC have reduced L-selectin; 2) T cells in tumor-free aged mice with elevated levels of MDSC have reduced L-selectin, and 3) peritoneal exudate T cells of tumor-free mice treated with plasminogen activator urokinase to elevate MDSC have reduced levels of L-selectin. MDSC are likely to down-regulate L-selectin through their plasma membrane expression of ADAM17 (a disintegrin and metalloproteinase domain 17), an enzyme that cleaves the ectodomain of L-selectin. Therefore, MDSC down-regulate L-selectin levels on naive T cells, decreasing their ability to home to sites where they would be activated. This is another mechanism by which MDSC inhibit antitumor immunity.
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PMID:Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. 1955 33

Local inflammation is a prominent characteristic of snakebite wound. Snake venom phospholipase A(2)s (PLA(2)s) are one of the main components which contribute to accumulation of inflammatory cells. We have isolated TM-N49 and promutoxin from Protobothrops mucrosquamatus venom and investigated their ability in induction of cell accumulation by using an in vivo mouse model. The results showed that both TM-N49 and promutoxin are potent stimuli for induction of neutrophil, lymphocyte, macrophage and eosinophil accumulation in the mouse peritoneum. The TM-N49- and promutoxin-induced inflammatory cell accumulation was inhibited by pretreatment of animals with cyproheptadine, terfenadine and Ginkgolide B, indicating that histamine and PAF is likely to contribute to the cells accumulation. Pre-injection of antibodies against adhesion molecules ICAM-1, CD18, CD11a and L-selectin showed that ICAM-1 is a key adhesion molecule of TM-N49- and promutoxin-induced lymphocyte, macrophage and eosinophil accumulation; CD18 and CD11a plays an important role in the migration of neutrophils, eosinophils and macrophages; and L-selectin is involved in the neutrophil and eosinophil accumulation. In conclusion, induction of inflammatory cell accumulation by TM-N49 and promutoxin confirms that group II PLA(2)s is pivotal stimulus for cell infiltration, through which they participate in the formation of snakebite inflammation.
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PMID:Induction of inflammatory cell accumulation by TM-N49 and promutoxin, two novel phospholipase A(2). 2053 12