Background. Macrophage procoagulant activity (PCA) has been proposed as a key mediator of abscess formation. Experimentally, transient systemic bacterial infections lead to increased numbers of intraabdominal abscesses after a subsequent episode of peritonitis. We tested the hypothesis that these events were regulated by classic major histocompatibility complex (MHC)-restricted antigen processing and presentation to lymphocytes followed by lymphocyte-mediated up-regulation of macrophage PCA. Methods. In vitro, macrophages and lymphocytes from BALB/c or C57BL/6 mice either untreated or preexposed to Escherichia coli were coincubated with bacteria or lipopolysaccharide. Cell lysates were tested for PCA in one-step clotting assay. In vivo, mice were either preexposed to E. coli or received passive transfer of lymphocytes from MHC-compatible or MHC-incompatible and naive or preexposed donors; peritonitis and intraabdominal abscesses were afterwards induced with E. coli, Bacteroides fragilis, and a sterile fecal adjuvant. Mice were killed after 10 days and were studied for abscess number and bacterial composition. Results. The presence of lymphocytes consistently increased macrophage PCA; lymphocytes from preexposed donors induced twice as much PCA as lymphocytes from naive donors regardless of MHC background. Both bacterial preexposure and passive transfer of lymphocytes from preexposed donors increased later intraabdominal abscess number in an MHC-restricted fashion. Conclusions. Transient infections enhance subsequent lymphocyte- mediated macrophage PCA, correlating with increases in abscess formation after peritonitis. The need for MHC identity to reproduce these results via passive transfer in vivo is consistent with classic T-cell receptor-mediated antigen presentation and lymphocyte activation before enhancement of PCA during peritonitis.
Bibliographical noteFunding Information:
Supported by University of Virginia Research and Development grant no. 5-507-RR05431-28. Accepted for publication Feb. 8, 1996. Reprint requests: Robert G. Sawyer, MD, 1500 E. Medical Center Dr., Department of Surgery, Division of Transplantation, 2926 Tanbman 0331, Ann Arbor, MI 48109-0331. Copyright 9 1996 by Mosby-Year Book, Inc. 0039-6060/96/$5.00+0 11/56/72754