Endotoxin-associated protein: interleukin-1-like activity on serum amyloid A synthesis and T-lymphocyte activation.
Bacterial endotoxins or lipopolysaccharides (LPS) elicit a variety of biologic activities in intact animals and various in vitro systems. LPS from most gram-negative bacteria have appeared to have similar biologic activities regardless of the species of origin or method of preparation of the LPS. More recent studies have suggested differences in the effects of protein-rich as opposed to protein-free LPS in inducing mitogenesis of lymphocytes from endotoxin-resistant C3H/HeJ mice. These studies examine other activities of endotoxin-associated protein (EAP), purified to less than 0.007% contamination with LPS, and demonstrate that this material has activity mimicking some of the effects of interleukin-1 (IL-1). EAP proved to be as potent as LPS in eliciting rises in concentrations of serum amyloid A (SAA) and was active in both endotoxin-sensitive (CF1) and endotoxin-resistant (C3H/HeJ) mice. In contrast to LPS, which mediates its SAA-inducing activity by release of an inducer (IL-1) from LPS-stimulated macrophages, EAP appeared to act directly to induce SAA production, in that incubation with macrophages failed to increase its activity. EAP also exhibited IL-1-like activity in the lymphocyte-activating factor assay when both CF1 and C3H/HeJ thymocytes and macrophages were tested. The lymphocyte-activating factor activity of EAP was not blocked by addition of polymyxin B. In addition, EAP exerted stimulatory activity on resting human T lymphocytes, costimulated with Sepharose-bound anti-CD3 monoclonal antibody 64.1, comparable to that observed with purified human monocyte IL-1. These studies indicate that proteins from procaryotic cells may act as cytokines for some eucaryotic cells.
Johns
M A
MA
Division of Infectious Diseases and Arthritis, Boston City Hospital, Massachusetts 02118.
Sipe
J D
JD
Melton
L B
LB
Strom
T B
TB
McCabe
W R
WR
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D002474:Cell-Free System; D004306:Dose-Response Relationship, Immunologic; D004355:Drug Stability; D004731:Endotoxins / Q000502:physiology*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007399:Interphase / Q000187:drug effects; D008050:Lipid A / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010447:Peptide Hydrolases; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D001426:Bacterial Proteins; D004731:Endotoxins; D007375:Interleukin-1; D008050:Lipid A; D000685:Serum Amyloid A Protein; C027315:lipid A-associated protein, Bacteria; D010447:Peptide Hydrolases