Enhancement of migration inhibitory factor activity by plasma esterase inhibitors.
The plasma esterase inhibitors alpha2-macroglobulin, alpha1-antitrypsin, C1-inhibitor, antithrombin-heparin cofactor, and, as previously described, soybean trypsin inhibitor (Kunitz) and diisopropylphosphorofluoridate (9) enhance the response of guinea pig macrophages to migration inhibitory factor. To obtain this effect, macrophages are incubated with inhibitors prior to assay. The data suggest that (a) the enhancement of migration inhibitory factor response is due to the inhibition of esterases associated with the macrophage through a distinct active site on the inhibitors, and (b) that the active sites of antithrombin-heparin cofactor and soybean trypsin inhibitor, which interact with the macrophage enzymes, are different from the active sites of these inhibitors which interact with thrombin and trypsin respectively. Chemical modification of the active site of antithrombin-heparin cofactor for thrombin and of soybean trypsin inhibitor for trypsin does not affect their capacity to enhance the migration inhibitory factor response. From studies with thrombin, it was known that antithrombin-heparin cofactor has a heparin binding site. Addition of heparin was found to prevent the migration inhibitory factor-enhancing effect of antithrombin-heparin cofactor. The present results suggest that plasma esterase inhibitors may play a regulatory role in the response of macrophages to mediators of cellular immunity.
D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology*; D007531:Isoflurophate / Q000494:pharmacology; D008214:Lymphocytes; D008259:Macroglobulins / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D000991:Antithrombins; D008259:Macroglobulins; D008263:Macrophage Migration-Inhibitory Factors; D000515:alpha 1-Antitrypsin; D007531:Isoflurophate; D006493:Heparin; D014360:Trypsin Inhibitor, Kunitz Soybean; D004950:Esterases