Submitted to: Journal of Leukocyte Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/8/1996
Publication Date: N/A
Interpretive Summary: One type of white blood cells that are often involved in the early immune response to infectious disease organisms are called macrophages. These cells have several functions, One is the production of soluble factors that, when released after the cells have become activated, kill microorganisms. One such factor is nitric oxide, and it has been shown to be produced and released from mouse macrophages. However, the production of nitric oxide from macrophages obtained from other species, including humans, has been controversial. In this study, we have demonstrated that macrophages obtained from the blood stream and spleen of cattle can be activated for the induction of nitric oxide production. It was also demonstrated that neutrophils, another type of white blood cell apparently is not programmed for this production. This study is important for a better understanding of what constitutes a successful immune response in cattle against invading pathogens. One such organism, Babesia bovis, a protozoan (one-celled animal) that causes a serious disease in cattle, and is the target pathogen in our overall plans to develop an improved vaccine. We have evidence to suggest that this parasite is susceptible to the effects of nitric oxide, which implies that the activation of macrophages will be an important element in the design of the vaccine.
Technical Abstract: Microbicidal activity of reactive oxygen intermediates and reactive nitrogen intermediates has been described from both murine and human cytokine activated macrophages. An L-arginine-dependent pathway of nitric oxide generation has recently been described from bovine bone marrow- derived macrophages. We have investigated the induction and release of both reactive oxygen intermediates and reactive nitrogen intermediates fro bovine neutrophils, blood monocytes, and resident spleen macrophages. Nitrite, as a measure of nitric oxide production, could not be induced from neutrophils under any stimulation conditions, while optimal conditions of induction from monocyte/macrophages required interferon-gamma as a primer for subsequent triggering by either tumor necrosis factor-alpha or lipopolysaccharide. Interferon-gamma also enhanced nitrite production after monocyte/macrophage ingestion of opsonized zymosan. L-arginine dependence was demonstrated by inhibition with an L-arginine analog and restoration with addition of excess exogenous L-arginine. In contrast, monocyte/macrophages were poor producers of hydrogen peroxide (a measure of reactive oxygen intermediate production) under conditions that caused release by neutrophils. Interferon-gamma did not enhance the release of hydrogen peroxide from stimulated neutrophils.