Studies on the inhibition of macrophage migration induced by soluble antigen-antibody complexes.
Mixtures of serum of Freund's complete adjuvant (FCA) immunized guinea-pigs and tuberculin PPD consistently inhibited the in vitro migration of peritoneal exudate cells (PEC) of normal guinea-pigs. It is shown that this inhibitory effect is due to a soluble complex between an IgG2 antibody and PPD. By separation of PPD on Sephadex G-200 two peaks were obtained, corresponding respectively to molecular weights of at least 800,000 and 25,000, separated by a plateau. Material derived from both peaks and from the plateau was able to form inhibitory complexes with anti-PPD IgG2. When a mixture of small molecular weight PPD and anti-PPD IgG2 was fractionated on Sephadex G-200, the inhibitory activity was recovered in the void region only. The detection of both IgG2 and PPD in the latter was taken as evidence for the presence of a high molecular weight antigen-antibody complex. When the mechanism of complex-induced inhibition of migration was examined it was found that: (1) complexes act directly on macrophages present in the peritoneal exudate; (2) removal of the Fc fragment of IgG2 by pepsin abolishes its ability to form migration inhibitory complexes; (3) passive sensitization of macrophages with anti-PPD IgG2, followed by exposure to PPD does not result in inhibition of migration; (4) in order to obtain migration inhibition, the complexes must be present during the entire migration period. A 2-hr pulse with complexes does not induce permanent inhibition; (5) the migration inhibitory activity of antigen--antibody complexes can be abolished by certain concentrations of puromycin and aminophylline.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D001202:Ascitic Fluid / Q000166:cytology; D002464:Cell Migration Inhibition; D002850:Chromatography, Gel; D005620:Freund's Adjuvant; D006168:Guinea Pigs; D007114:Immunization; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008970:Molecular Weight; D011691:Puromycin / Q000494:pharmacology; D014373:Tuberculin; D005719:gamma-Globulins
D000906:Antibodies; D000936:Antigen-Antibody Complex; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D014373:Tuberculin; D005719:gamma-Globulins; D000628:Aminophylline; D011691:Puromycin; D005620:Freund's Adjuvant