Enhancement of lymphocyte response to PHA by lysosomal enzymes from polymorphonuclear leukocytes of RA joint fluid. I. Biological effect on T lymphocyte function.
The effect of polymorphonuclear leukocyte (PMN) granule lysates obtained from joint fluid of RA on the in vitro DNA synthesis of PHA-stimulated autologous lymphocytes from joint fluid was studied. Lymphocytes were cultured for 3 days with or without PMN lysates in 2 ml of RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum (FCS). The lymphocytes were stimulated with phytohemagglutinin (PHA-M). The DNA synthesis was measured by counting the [3H]thymidine incorporation. Lymphocytes from RA joint fluid stimulated with PHA-M showed 19,466+/-987 cpm (mean+/-SE) per 10(6) cells in the absence of PMN lysates. Upon addition PMN lysates to the PHA-stimulated lymphocytes, the maximum in vitro DNA synthesis increased to 44,877+/-1338 cpm. The enhancing effect of PMN lysates was abolished by plasma inhibitors or by passage through a column of protease inhibitor (Trasylol). It was concluded, therefore, that the enhancing effect of PMN lysates on PHA-stimulated lymphocytes may be associated with lysosomal proteases. Based on experiments using separated T and B lymphocytes, the enhancing effect of PMN lysates was considered to result from the activation of T lymphocytes. The results obtained in the present study suggest an important role for lysosomal proteases in the perpetuation of rheumatoid synovitis.
D000017:ABO Blood-Group System / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000097:blood; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000201:enzymology*; D009504:Neutrophils / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology*
D000017:ABO Blood-Group System; D004247:DNA