Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages have been isolated from ascitic and collagenase-dispersed tumours from patients undergoing surgery for ovarian cancer. Macrophages were present in varying proportions in both sites, though the ration of macrophages to tumour cells was higher in ascites. Marked variation in size (as detected by sedimentation velocity) and cytochemical markers in the macrophages was noted. Highly enriched macrophage fractions were isolated from the ascites and collagenase-dispersed solid tumours by a combination of sedimentation velocity and selective EA RFC or adherence techniques. Suppressor activity in the PHA assay was detected in tumour macrophages (4/10 giving less than 50% inhibition), ascitic macrophages (1/15) and blood monocytes (2/7). Lymphocyte fractions from tumours were unresponsive to PHA and failed to suppress the blood response. Suppressor activity was also present in the purified tumour-cell fraction of 6/14 patients. ADCC activity was tested in a few patients. When the activity was determined against the SB target cells, tumour-derived macrophages were inactive, whereas the ascitic fraction showed low but significant activity which averaged much lower than patients blood values. The ADCC assays carried out with the CRC target cell indicated activity within the range of patient blood values in 4/4 ascites and 2/4 tumour macrophage fractions. Cytotoxicity was also assessed against co-purified autologous tumour cells. Although activity was detected in many of the tests, the results seemed to reflect target cell sensitivity. There appeared to be a correlation between cytotoxicity with test macrophages and normal blood mononuclear cells. The results indicate that the cytochemical heterogeneity and the variation in size between macrophage fractions is associated with a spectrum of activities.
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PMID:Mononuclear-cell infiltration in ovarian cancer. III. Suppressor-cell and ADCC activity of macrophages from ascitic and solid ovarian tumours. 621 Nov 87

We have shown that two of the matrix metalloproteinases (MMPs), matrilysin and stromelysin-1, are capable of cleaving all of the human IgG subclasses. The cleavage occurs at a conserved site in the CH(2) domain of the heavy chain of IgG, releasing a single chain Fc-like fragment. We have not been able to demonstrate cleavage of IgA, IgD, IgM or IgE classes, which lack the cleavage site, nor could we show cleavage of IgG by collagenase, gelatinase, macrophage metalloelastase or membrane-type (MT)-MMP. This cleavage of IgG, by separating the antigen-binding (Fabprime prime or minute)(2) from the Fc portion, will remove much of the immunoglobulins' functionality, e.g. complement fixation, Fc receptor binding. In the context of a tumour producing matrilysin or stromelysin, this may represent a way in which the tumour protects itself from ADCC. In inflamed or damaged tissues where plasma protein leakage occurs, degradation by MMPs may be a mechanism for clearance of IgG.
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PMID:Selective cleavage of human IgG by the matrix metalloproteinases, matrilysin and stromelysin. 1184 44

A zinc containing metalloprotease, 175 kDa collagenase, purified from adult female Setaria cervi showed strong cross-reactivity with sera from putatively immune (PI) individuals (unpublished observation) and induced cytotoxicity to B. malayi L3 larvae and microfilariae by ADCC mechanism [Srivastava Y, Bhandari YP, Reddy MVR, Harinath BC, Rathaur S. An adult 175 kDa collagenase antigen of Setaria cervi in immunoprophylaxis against Brugia malayi. J Helminth 2004;78:347-52]. These preliminary observations suggested the immunoprotective nature of collagenase. To confirm the vaccine potential of this protease, a vaccine trial was conducted in jirds (Meriones unguiculatus) against human filarial parasite B. malayi. The vaccination resulted into a mean protection level of 75.86% and produced high level of protease neutralizing antibodies. Cytokine analysis in immune jirds sera suggested a mixed Th1/Th2 type cellular immune response whereas ELISA, immunoblotting and enzyme antibody inhibition assay revealed the presence of specific anti-collagenase antibodies. Taken together, all these results suggest that S. cervi 175 kDa collagenase could form the basis of an effective molecular vaccine against human lymphatic filariasis.
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PMID:Vaccination with Setaria cervi 175 kDa collagenase induces high level of protection against Brugia malayi infection in jirds. 1687 Mar 14