The effects of the sulfydryl donor drug N-(2-mercaptopropionyl)-glycine (MPG) on neutrophil chemotaxis, adhesiveness, phagocytosis, and hexose monophosphate shunt activity were investigated in vitro. The drug significantly enhanced all the neutrophil functions tested when used at appropriate concentrations. The results, which are in accord with the well known inhibition of neutrophil function by sulfydryl-blocking agents, suggest the possible therapeutic usefulness of the drug in clinical conditions with defective neutrophil function.
Human neutrophils, triggered by Concanavalin A, were cytotoxic against chicken red blood cell targets as determined by the 51Cr release method. The cytolysis increased with the effector: target ratio, reaching optimal levels when 2-4 neutrophils were available for each chicken red blood cell. The target cell lysis required an optimal release of highly reactive oxygen by-products by neutrophils, since neutrophils from a patient with chronic granulomatous disease failed to exhibit any cytolytic activity. Superoxide dismutase, catalase and inhibitors of heme-containing peroxidases (azide and cyanide) significantly inhibited the neutrophil-mediated cytotoxicity. Together these results indicate that superoxide anion and the myeloperoxidase-hydrogen peroxide system are simultaneously involved in the target cell injury by Concanavalin A-triggered neutrophils.
A monoclonal anti-idiotyped antibody (IgG1k MAb 3B11D4) has been raised against the lambda-chain dimers isolated from the urine of a patient (DEP) with AL amyloidosis. This antibody binds a conformational idiotope present on the monoclonal DEP IgA, but does not recognize the reduced and alkylated lambda-chain monomers, nor the 15- to 17-kDa light chain fragments obtained from the amyloid fibrils, which have the same N-terminal sequence as the urinary light chains. The nonreactivity of this MAb with amyloid fibrils was confirmed by immunohistochemical examination of cryostatic sections of an amyloidoma surgically removed from the patient's subcutaneous tissue. Our data demonstrate that the deletion of about 70 amino acid residues of the C-terminus of the lambda chain prevents the formation of the self-limiting dimer and may facilitate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning and cytotoxicity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral blood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total body irradiation, and rescue with circulating stem cells. These antibodies could be used in two distinct phases: first, in the purging of the stem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.