Endotoxin-associated protein: a potent stimulus for human granulocytopoietic activity which may be accessory cell independent

Abstract

Proteins coextracted with endotoxin, termed endotoxin-associated protein (EAP), have been shown to exert interleukin 1-like activities. The present studies demonstrate that EAP also exerts potent granulopoietic colony-stimulating activity (CSA) on human peripheral blood and bone marrow progenitor cells, comparable to that seen with various types of conditioned media. The CSA observed with EAP appeared to be heat (100°C, 30 min) and trypsin resistant and partially pronase resistant. Similar resistance was observed with the porin proteins of the outer membrane of gram-negative bacteria, and similar CSA activity was observed with a purified porin preparation of Neisseria gonorrhoeae. The CSA of EAP could be demonstrated in human peripheral blood and bone marrow leukocytes rigorously depleted of monocytes, T lymphocytes, and B lymphocytes by treatment with specific monoclonal antibodies and complement.

Neisseria gonorrhoeae Porin Modifies the Oxidative Burst of Human Professional Phagocytes

“…LPS is considered to favor the trimerization of gonococcal porin and to be essential for the insertion of porin into mem-branes as was previously reported for the Escherichia coli outer membrane protein PhoE (13,34). However, endotoxin-associated proteins are known to be potent stimuli for human phagocytes (9). Thus, we favor an explanation in which LPS facilitates the priming of neutrophils by porin.…”

Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis.

“…These findings have been largely confirmed by Porat et al (173), who isolated LAP from E. coli. However, these workers reported that in contrast to the studies of Johns and coworkers (12,104), T cells partially mediated the effect of the LAP and that the formation of granulocyte/macrophage colonies induced by LAP could be blocked by a neutralizing antiserum to IL-1␤. Porat et al also reported that the active protein in the LAP preparation had a molecular mass of 17 kDa (173).…”

“…LAP were also found to be active in the lymphocyte-activating factor assay and to act as a costimulatory factor for the proliferation of resting human T lymphocytes. LAP were also shown to be capable of inducing the formation of granulopoietic colonies when added to human peripheral blood and bone marrow progenitor cells which had been depleted of accessory cells (monocytes and T and B lymphocytes) (12). These workers also confirmed the great stability of the LAP inasmuch as heating to 100ЊC for 30 min or exposure to trypsin or pronase for 24 h at 37ЊC did not decrease the biological activity of these proteins.…”

Lipid A‐associated proteins from Porphyromonas gingivalis stimulate release of nitric oxide by inducing expression of inducible nitric oxide synthase

“…The proteinaceous components of endotoxin, known as lipid A‐associated proteins or endotoxin‐associated proteins, are a family of proteins that bind to lipopolysaccharide in the cell wall of gram‐negative bacteria (1). The lipid A‐associated proteins were first recognized when it was discovered that the B‐cell mitogenic activity of Escherichia coli endotoxin in the lipopolysaccharide‐unresponsive C3H/HeJ mouse depended on the protein content of the endotoxin (2).…”