Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using immunohistochemical techniques and a large number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of macrophages (MOs) and dendritic cells in human spleen were assessed. The results of this study show that different subsets of MOs and dendritic cells are present in the spleen and that some of these occupy discrete microanatomic locations. In the red pulp (RP) certain antigens are expressed by different proportions of uniformly distributed MOs in the cords. On the other hand, some antigens are present on MOs that form clusters of variable size within the red pulp. These include CD11c, CD15 and alpha-1-anti-chymotrypsin. Another type of cell in the RP that is phagocytic under certain conditions is the splenic sinusoidal lining cell (SLC). These cells exhibit a phenotype that is unique: nonspecific esterase (NSE)+, lysozyme+, and HLA-DR+, CD36+, factor VIII-related antigen+, CD8+ and CD71+. MOs in the splenic marginal zone (MZ) share some antigens with red pulp MOs, but in addition express CD11b, CD14 (Mo2;63D3) and 61D3. These antigens are found on only a few RP MOs. MZ cells expressing one antigen shared with RP MOs (CD4) and one present largely on the MZ cells (CD14;63D3) form clusters around small vessels; these structures resemble the so-called splenic ellipsoids that may play a role in the trapping of circulating antigens. Phagocytic MOs (tangible body MOs) of the white pulp follicular germinal centers were also shown to differ from RP and MZ cells with respect to the expression of the antigens CD11b, CD14 (Leu M3;Mo2), CD16 and the antigen detected by antibody 25F9. The unique topographical and surface antigenic features of dendritic cells were confirmed by this study. Furthermore, these cells were found to share a number of antigens with RP, MZ, and white pulp MOs, which suggests that they may be derived from a common progenitor. The presence of phenotypic subpopulations and variation in distribution among human splenic phagocytic cells and dendritic cells may be indicative of functional specialization.
 ...
PMID:Phenotypic subpopulations of macrophages and dendritic cells in human spleen. 205 20

The effects of the inflammatory mediators lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF) and unstimulated and activated neutrophils (PMNs) on endothelial cell (EC) necrosis were studied using the cultured human EC line (ECV-304) and human PMNs in vitro. LPS and TNF alone or their combination failed to induce EC necrosis. Activated PMNs, as evidenced by augmentations in CD11b expression and respiratory burst, induced significant EC necrosis commencing at 12 hr of coculture, which was strongly dependent on the ratio of PMN:ECs and the duration of PMN:EC coculture. In contrast, unstimulated PMNs induced no significant increases in EC necrosis. To examine the mechanisms of activated PMN-mediated EC necrosis, the oxygen radical scavengers superoxide dismutase (SOD) and catalase, as well as the protease inhibitors phenylmethylsulfonyl fluoride (PMSF), alpha 1-antitrypsin (alpha 1-AT), soybean trypsin-chymotrypsin inhibitor (TCI), and aprotinin, were studied in coculture experiments. EC necrosis induced by activated PMNs could be markedly attenuated by SOD, PMSF, alpha 1-AT, TCI, aprotinin, or their combinations. Although aprotinin enhanced respiratory burst, this agent inhibited necrosis by downregulating PMN CD11b and PMN-EC adhesion. These results demonstrate that the inflammatory mediators LPS and TNF and quiescent PMNs fail to induce EC necrosis. However, PMNs activated by inflammatory mediators can induce EC necrosis through oxidative and nonoxidative mechanisms and this process is dependent on PMN-EC adhesion.
 ...
PMID:Mechanisms involved in the induction of human endothelial cell necrosis. 859 44

In the present study we investigated the modulation of the polymorphonuclear neutrophil (PMN)-endothelial cell adhesion process by the two main proteinases released from activated PMN during their adhesion to endothelium. Our results showed that, in contrast with elastase, cathepsin G was a powerful inhibitor of PAIN adhesion to interleukin-1 (IL-1)-treated human umbilical vein endothelial cells. This inhibitory effect was linked to the enzymatic activity of the proteinase and was selectively directed against PMN. Because the viability and the reactivity of PMN were not modified by cathepsin G, we looked for a possible effect on adhesion molecules. L-selectin was not cleaved by cathepsin G, whereas it was by chymotrypsin, a closely related proteinase. Cathepsin G blocked PMN adhesion to activated endothelial cells, but also to serum- or fibrinogen-coated plates, three adhesion processes mediated by CD11b/CD18. However, by FACScan analysis or by immunoprecipitation, we failed to find evidence of modifications of CD11b/CD18 expression. Although the precise molecular target(s) of cathepsin G remain(s) to be defined, these data indicate that this proteinase, which is known as an inflammatory mediator, can also be considered as a potential down-regulator of adhesion reactions involved in the inflammatory process.
 ...
PMID:Inhibition of neutrophil-endothelial cell adhension by a neutrophil product, cathepsin G. 869 Oct 71