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Goat antibodies to pig lung angiotensin-converting enzyme (kininase II) were conjugated to microperoxidase. Rat lung tissue, previously incubated with non-immune goat serum, was incubated with the antibody-microperoxidase conjugate and then with H2O2 and 3,3-diaminobenzidine. Electron microscopy revealed reaction product on the plasma membrane and caveolae of endothelial cells, especially those of capillaries and venules. These results support the hypothesis that angiotensin I and bradykinin are metabolized by enzymes on the luminal surface of pulmonary endothelial cells.

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Objective. The complement component C1s is present in dog joint fluid in an activated state. Since C1s degrades insulin-like growth factor binding protein 5 (IGFBP-5), we undertook to determine whether inhibiting C1s in joint fluid would result in an increase in the amount of intact IGFBP-5 and IGF-1 in cartilage and joint fluid, and whether C1s inhibition would be associated with a reduction in cartilage destruction during the development of osteoarthritis (OA).Methods. Twenty-two dogs were randomized to 3 treatment groups. All dogs underwent anterior cruciate ligament transection and were exercised. Dogs received 1 of 3 treatments: buffer alone (controls; n ‫؍‬ 6); PB-145, a peptide derived from the sequence of antithrombin III (n ‫؍‬ 9); and pentosan polysulfate (PPS; n ‫؍‬ 7). PB-145 or saline was injected into the joint space 3 times per week for 3 weeks. PPS was injected intramuscularly weekly for 3 weeks.Results. Joint histology showed preservation of chondrocytes and a smooth joint surface in the animals treated with PB-145 and PPS. Mankin scoring showed statistically significant reductions in joint destruction with PB-145 and PPS treatments (P < 0.01) compared with buffer control. Mean active collagenase concentrations were decreased by these two treatments. Immunoblotting of joint fluid showed that both treatments increased concentrations of intact IGFBP-5. Direct analysis of IGFBP-3 and IGFBP-5 protease activity showed that IGFBP-5 was degraded more rapidly and that PB-145 and PPS inhibited the degradation of both proteins. Total IGF-1 concentrations in joint fluid were increased 5.6-5.8-fold by these two treatments. Analysis showed that C1s was being activated in joint fluid and that its activation was inhibited by the addition of PB-145 or PPS.Conclusion. The findings suggest that direct inhibition of the serine protease C1s results in increased concentrations of intact IGFBP-5 and that proteolysis of IGFBP-3 is also inhibited, probably by the inhibition of some other protease. This increase in concentrations of intact IGFBP-3 and IGFBP-5 leads to an increase in IGF-1 which is associated with an improvement in joint architecture during the development of OA.The insulin-like growth factors (IGFs) were discovered because of their ability to stimulate sulfate incorporation into cartilage, and they were later proven also to stimulate cartilage growth (1). More recently, it has been shown that chondrocytes synthesize and secrete IGF-1 and that anti-IGF-1 antibodies can inhibit chondrocyte growth (2,3). The role of locally synthesized IGF-1 has also been analyzed by directly injecting growth hormone (GH) into the growth plate of hypophysectomized animals, which results in increases in stimulation of cartilage growth and IGF-1 synthesis (4). Administration of anti-IGF-1 antibody blocks this stimulatory effect of GH injection, suggesting that much of its effect is mediated by locally produced IGF-1 (3,5). This hypothesis has received further support by recent gene deletion experiments showing that if IGF-1 ...