Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The determinant specificities of five monoclonal anti-fibronectin antibodies, designated BC7, CE9, BD4, AB3 and CPG1, were defined and mapped within intact human plasma fibronectin by immunoblot analyses with defined fragments of fibronectin. The latter were derived by tryptic, chymotryptic or cathepsin D digestion of the intact molecule and fractionated by DE-cellulose chromatography and gelatin and/or heparin affinity chromatography. Monoclonal BC7 recognizes intrachain disulphide-formed determinants within the 27,000 MW N-terminal domain; monoclonal CE9 recognizes determinants within an 18,000 MW fragment immediately adjacent to the carboxyl end of the gelatin-binding domain; monoclonal BD4 recognizes determinants within the cell-adhesive domain and within 150,000 of the N-terminus; monoclonal AB3 recognizes intrachain disulphide-formed determinants within 35,000 of the COOH-terminus of the intact molecule and detectable only on the alpha-chain polypeptide subunit; and monoclonal CPG1 recognizes determinants present on both chains of the intact molecule and immediately adjacent to the interchain disulphide bonds at the COOH-terminus. None of the epitopes recognized by these monoclonal antibodies is present at alternative regions of the intact molecule. Fab fragments of each of these monoclonal antibodies were incubated with gelatin-coated sheep erythrocytes which had been reacted with a fixed amount of intact plasma fibronectin. When these target particles were incubated with monolayers of human monocytes and the resultant rosettes were quantitated, the Fab fragments of BD4 markedly inhibited the proportion of monocytes binding these fibronectin-bearing targets, whereas none of the other Fab fragments had an inhibitory effect. Thus, monocyte fibronectin receptors which mediate adherence of fibronectin bridges to a target via gelatin recognize regions within the cell-adhesive domains of intact fibronectin but not regions at the amino or carboxy terminals.
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PMID:Identification with monoclonal antibodies of different regions of human plasma fibronectin, including that which interacts with human monocyte fibronectin receptors. 257 23

The functional opsonic and monocyte adherence domains within the 180,000 m.w. opsonic fibronectin fragment (180K-opFnf) that selectively augments human monocyte phagocytosis of particulate activators of the alternative complement pathway were analyzed with Fab fragments of monoclonal anti-fibronectin antibodies BC7, CE9, BD4, AB3, and CPG1, and with fragments of intact human plasma fibronectin derived by cathepsin cleavage and isolated by affinity chromatography. Monoclonals AB3 and CPG1, which recognize epitopes within 40,000 daltons of the carboxy terminus of intact fibronectin, and the cathepsin D-derived, disulfide-linked fragments that contain these epitopes each inhibited the opsonic function of 180K-opFnf. Monoclonals AB3 and CPG1 inhibited monocyte ingestion of rabbit erythrocytes (Er) by 60 and 50%, respectively, when 180K-opFnf was pretreated with 20 micrograms of these monoclonals, but neither monoclonal affected the enhanced monocyte ingestion of Er pretreated with the fibronectin fragment. The pretreatment of Er with 5 micrograms and 40 micrograms of the disulfide-linked, cathepsin D derivatives isolated from high and low affinity heparin fractions, respectively, inhibited the proportion of ingesting monocytes by 60%, but these types of fragments had little effect when concurrently incubated with the opsonic fragment and Er. Monoclonals CE9 and BD4, which recognize epitopes located adjacent to or within the cell-adhesive domain of intact fibronectin, respectively, inhibited the monocyte adherence function of 180K-opFnf, as evidence by their comparable inhibitory effects when present before or after Er were opsonized with 180K-opFnf. When 20 micrograms of monoclonals CE9 and BD4 were each introduced before and after Er were opsonized with 180K-opFnf, monocyte ingestion was inhibited by 60 and 65% and by 51 and 60%, respectively. At 42 micrograms, cathepsin D-derived, non-gelatin-binding, low affinity heparin fragments that contained both BD4 and CE9 determinants or only the BD4 determinant inhibited monocyte ingestion by 53 and 74%, respectively, when concurrently incubated with 180K-opFnf and target Er, but were without effect when used to pretreat Er before the addition of 180K-opFnf. Thus, the inhibitory effects produced by monoclonals AB3 and CPG1 and by cathepsin D-derived, disulfide-linked fragments containing their corresponding epitopes demonstrated that the opsonic domain within 180K-opFnf is immunologically similar to regions within the carboxy terminus of intact plasma fibronectin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization of the opsonic and monocyte adherence functions of the specific fibronectin fragment that enhances phagocytosis of particulate activators. 396 34