The Effects of CD11c/CD18 and CD14 Blocking on Lipopolysaccharide-induced Endotoxemia

ABSTRACT

We studied the morphologic changes and the expression of cytokines of major organs by blocking CD14 and CD11c/CD18, which are known to be receptors of lipopolysaccharide (LPS), in the LPS induced endotoxemic mice. In 2 and 8 hours after initial intraperitoneal injection of 10 mg/kg of LPS into the mice, 500 microgram/kg of anti-CD14 antibody (Ab) and/or the same dosage of the anti-CD11c/CD18 Ab were administered intravenously, respectively or concomitantly. Under the light microscope, the LPS only and the LPS with the anti-CD14 Ab injected groups (group 1 and 2) showed marked acute inflammation in the organs, especially in the lung and liver, but the LPS with the anti-CD11c/CD18 Ab only or with both anti-CD14 and anti-CD11c Abs injected groups (group 3 and 4) revealed only mild acute inflammation. Under the electron microscope, there was marked inflammation in the group 1 and 2 such as marked infiltration of neutrophils, monocytes/ macrophages, lymphocytes, aggregation of platelets, and marked edematous change of endothelial cells with separation from the basement membrane. However in the group 3 and 4, there was only mild inflammation such as mild infiltration of neutrophils in the tissue or aggregation of neutrophils in the capillaries and sinusoids with mild endothelial swelling. The expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha (IL-1alpha), detected by RT-PCR method, was remarkable in the group 2, but minimal in the group 3 and 4. We conclude that blocking the CD11c/CD18 with anti-CD11C/CD18 Ab is effective for the prohibition of biologic reactions and diminution of the inflammation induced by the LPS, even in the LPS induced endotoxemia.