Biomedical subjects
Publications and source records attributed to T L Vischer.
Some results concerning the stimulatory effect of proteases on lymphocytes and other cells such as Hela cells and fibroblasts are evaluated. Preliminary evidence indicates that such stimulating factors are indeed released from cells during phagocytosis and can be inhibited by aprotinin. The potential role of such proteases in inflammation is discussed.
Suramin, a drug against trypanosomiasis and onchocerciasis, stimulates in vitro mouse B-lymphocytes to transform into blastcells, to incorporate 3H-thymidine and to go into mitosis. Thymus cells (hydro-cortisone-sensitive or resistant) do not respond whereas cells from homozygous nude mice are stimulated. The large majority of the blast-cells have surface immunoglobulins, and the proportion of cells with intracellular immunoglobulin increases during the course of the cultures.
Dibutyryl-cyclic adenosine 3'5'-monophosphate (cAMP) added to mouse spleen cell cultures under serum free conditions inhibited the stimulation of [3H]thymidine incorporation induced by T-cell mitogens much more than the one induced by B-cell mitogens. The inhibition was most impressive with phytohaemagglutinin, followed by concanavalin A, pokeweed mitogen and the specific antigen Keyhole limpet haemocyanin (KLH). The response to bacterial lipopolysaccharide (LPS) was clearly less susceptible to suppression and the effect on the stimulation induced by trypsin and suramin, both B-cell mitogens, was marginal. Similar results were obtained by addition of isoproterenol or therophyllin to the cultures.
Trypsin, a neutral protease, enhanced the direct plaque response of T cell-suffiecient mouse spleen cell cultures to sheep erythrocytes (SRBC) and significantly increased the number of spontaneous PFC against SRBC in cultures without antigen. Moreover, trypsin proved to be able to substitute for T cells in nu/nu spleen cell cultures stimulated with SRBC. Its restorative capacity in this type of response was comparable to the one of lipopolysaccharide. Restoration of antibody synthesis in T cell-deprived cultures could not be explained by enzymatic alteration of SRBC. The data are discussed in terms of a possible role of hydrolytic enzymes released by accessory cells during the induction of an antibody response.
Using an assay of macrophage migration, where the cells emigrate from an agarose droplet, it was found that the neutral proteases trypsin, chymotrypsin, Pronase and elastase have MIF-like activity. Appropriate enzyme inhibitors counteract this effect. To twelve synovial fluids from patients with inflammatory arthritis, which have MIF-like activity (migration index between 0-3 and 0-7) protease indhibitors (Trasylol, ovomucoid and soybean inhibitor) were added. Ten of the fluids lost some of their MIF-like activity with at least one inhibitor. Phenylmethylsulphonylfluoride counteracted totally the MIF-like activity of the two fluids tested. It is concluded that MIF-like activity of inflammatory synovial fluids is due, at least partially, to proteases.
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A destructive arthropathy is much more common when generalized osteoarthritis (GOA) and articular chondrocalcinosis (ACC) coexist than in GOA alone. Fifty-two patients with GOA and ACC were compared to a matched control group with GOA alone. A marked increase in the frequency of a destructive arthropathy was found in the group with both GOA and ACC. Nonweight-bearing joints were often involved in the group with GOA and ACC, whereas they were seldom involved in the group with GOA alone.
BALB/c spleen cells (5 x 10(6)) were cultured in 1 ml of serum-free RPMI 1640 medium for 3 days in order to examine the effect of cholera enterotoxin (CN) and its spontaneously formed toxoid (CD) on lymphocyte stimulation. Stimulation was assessed after addition of [3H] thymidine for the last 16 hours of culture. One microgram of CN per culture markedly reduced the baseline of [3H] thymidine incorporation and the stimulation due to phytohaemagglutinin (PHA), concanavalin A (con A) and bacterial lipopolysaccharide (LPS). One microgram of CD diminished the base-line to half, abolished the response to PHA, reduced the response to con A and had very little effect on the LPS-induced stimulation. One-tenth the amount (0-1 mug) of both CN and CD affected only the PHA reaction. A secondary response to haemocyanin in vitro was not decreased by this lower dose. The effect of 1 mug on CN on the LPS response could be reduced by pretreatment of the cells with CD, whereas the PHA reaction remained markedly diminished. Dibutyryl-cAMP added to culture tubes had a similar effect ot 1 mug of CN, affecting the PHA response much more than the response to LPS. Spleen cells of mice immunized with CD gave a significant proliferative response to both 1 mug of CD and CN. The results are interpreted as indicating a strong inhibitory effect of CN mediated by accumulation of intracellular cAMP. CD-immunized cells contain specific receptors for both CD and CN which probably compete with the sites responsible for adenylate cyclase stimulation by CN.
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