Distribution and immunoregulatory properties of antisecretory factor

Abstract

Inflammatory processes and the mechanisms by which they are initiated and controlled within the central nervous system (CNS) involve a vast array of cell types and molecules. One cell type believed to be involved in the control of inflammation in the CNS is the microglial cell. The TLD antibodies are a panel of monoclonal antibodies reactive to rat microglial antigens. One antibody from this panel, clone TLD-1A8A, is specific for antisecretory factor (ASF). ASF is a previously identified protein characterized as a potent inhibitor of enterotoxin-induced intestinal fluid secretion. Our results extend the function of this molecule to include the regulation of immune reactions. Administration of TLD-1A8A to T-cell proliferation or mixed leukocyte response assays resulted in increased proliferation of T cells. Flow cytometric analysis indicates that ASF is expressed on macrophages, B cells and dendritic cells, but not on T cells or granulocytes. Immunohistochemical analysis indicates that ASF is expressed by macrophages and cells of dendritic morphology in the spleen, thymus, lymph nodes, Peyer's patch, and in the perivascular area in the CNS. Furthermore, Western blot analysis indicates that ASF is expressed in many tissues including all secondary lymphoid organs. These data suggest that ASF may have a previously unsuspected role in regulating the immune system.

Antisecretory factor as a potential health-promoting molecule in man and animals

“…T cell proliferation assays performed with rat serum containing AF showed that AF blocked the TLD-1A8A effect on T cells, suggesting a role for AF in the regulation of T cell responses (8) . However, the effects on the immunological response observed in vitro did not clarify the nature of the interaction between AF and its antibody.…”

“…In situ hybridisation and immunohistochemical analysis has demonstrated that AF is expressed in various mammalian organs (3,8) . Monoclonal TLD antibodies, obtained from rats immunised with cultured microglial cells, were screened by Davidson & Hickey (8) with the aim to investigate the roles of perivascular and microglia cells in the inflammatory processes in the CNS.…”

“…The immunohistological distribution of AF suggests that this protein may play a role in the immune system as an anti-inflammatory agent (8) . In rat jejunal loops, AF inhibited the inflammatory response caused by toxin A from Clostridium difficile (4) .…”

An Experimental Model of Autoimmune Pancreatitis in the Rat

“…The staining procedure has been detailed elsewhere. 9 After a 30-second exposure to absolute methanol at Ϫ20°C and extensive rinsing in 0.5 mol/L Tris buffer (pH 7.6), the sections were incubated with appropriate primary antibodies at 4°C overnight. After further buffer washes, the slides were incubated with biotinylated secondary anti-murine IgG antibodies (Vector Laboratories, Burlingame, CA) for 40 minutes, washed in buffer, and then incubated with avidin-biotinylated horseradish peroxidase complex (Vector Laboratories) for 2 hours.…”

Therapeutic effect of antisecretory factor-rich egg yolk on the late phases of 2,4,6-trinitrobenzenesulphonic acid colitis in mice

“…In addition, AF-treated animals showed a significant decrease in the colonic production of pro-inflammatory cytokines, IL-1 and IL-2, as well as the powerful chemotactic agent LTB 4 . AF treatment was also associated with a small but significant increase in PGE 2 levels at week 2 after TNBS administration.…”