The Effect of Some Protease Substrates and Inhibitors on Chemotaxis and Protease Activity of Human Polymorphonuclear Leukocytes

Abstract

Endotoxin (lipopolysaccharide, LPS) has been found to act on all three cell types of the immune system, thymus-derived (T-) cells, bone marrow-derived (B-) cells, and macrophages. LPS is mitogenic for B-Iymphocytes and activates them to release a chemotactic lymphokine. Macrophage activation appears to be mediated by macrophage-activating factor, another lymphokine released from B-cells. In addition, LPS acts synergistically with phytohemagglutinin to initiate division of purified T-Iymphocytes. All these phenomena are mediated by the lipid A moiety of LPS. The role of lymphoid cells in mediating the lethal effects of LPS have also been investigated. The adoptive transfer of spleen cells from LPS-responsive mice (C3H/HeN) to LPS-resistant but histocompatible mice (C3H/HeJ) rendered the LPS-resistant mice significantly more susceptible to LPS-induced lethality. These findings suggest that spleen cells play an essential role in mediating the lethal effects of LPS in vivo.