A low molecular weight, heat-labile factor enhances neutrophil Fc receptor-mediated lysosomal enzyme release and phagocytosis.
When exposed to solid-phase immune complexes, polymorphonuclear neutrophils (PMN) degranulate and release proteases capable of degrading the major structural macromolecules of the joint. Evidence indicates that the PMN response to such activators may be modified by factors present at the sites of inflammation. We have evaluated the effects of a low molecular weight factor present in synovial fluid from rheumatoid arthritis (RA) patients on Fc receptor-mediated PMN degranulation and phagocytosis. Synovial fluid samples from 11 RA patients were studied; 10 of them contained factor(s) which augmented phagocytosis and degranulation mediated through the Fc receptor. This factor(s) alone, however, did not initiate neutrophil degranulation: its MW is less than 10,000 daltons and it is unstable when heated to 56 degrees C. We also examined supernatants that were produced by coculturing adherent human mononuclear cells stimulated by IgG-coated sheep red blood cells with autologous nonadherent mononuclear cells. A factor(s) with properties similar to those found in the synovial fluids (i.e., heat-labile at 56 degrees C and capable of augmenting Fc receptor-mediated degranulation and phagocytosis) was found in the stimulated human mononuclear cell culture supernatants. Filtration studies indicated that the MW of this factor(s) is between 2,000 and 10,000 daltons. No such activity was detected in culture supernatants of unstimulated mononuclear cells. Production of the cytokine was blocked by cycloheximide, indicating that protein synthesis was necessary. This factor(s), by enhancing PMN degranulation, may augment PMN-mediated tissue destruction in diseases such as RA.
Blackburn
W D
WD
Division of Clinical Immunology and Rheumatology, Birmingham Veterans Administration Hospital, AL 35233.
Heck
L W
LW
Koopman
W J
WJ
Gresham
H D
HD
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology; D001688:Biological Products / Q000032:analysis / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines; D004355:Drug Stability; D006358:Hot Temperature; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D008970:Molecular Weight; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013582:Synovial Fluid / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D015054:Zymosan / Q000494:pharmacology
D001688:Biological Products; D016207:Cytokines; D011961:Receptors, Fc; D015054:Zymosan; D003513:Cycloheximide