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Title: COMPARATIVE NITRIC OXIDE PRODUCTION OF LPS-STIMULATED MONOCYTE-DERIVED MACROPHAGES FROM OVIS CANADENSIS AND OVIS ARIES

Author
item Sacco, Randy
item Waters, Wade
item RUDOLPH, KAREN - IDAHO DEPT OF FISH & GAME
item DREW, MARK - IDAHO DEPT OF FISH & GAME

Submitted to: Comparative Immunology Microbiology and Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2005
Publication Date: 2/7/2006
Citation: Sacco, R.E., Waters, W.R., Rudolph, K.M., Drew, M.L. 2006. Comparative nitric oxide production of LPS-stimulated monocyte-derived macrophages from Ovis canadensis and Ovis aries. Comparative Immunology Microbiology and Infectious Diseases. 29(1):1-11.

Interpretive Summary: Bighorn sheep are more susceptible to certain bacterial infections than are domestic sheep. We hypothesized that the differences between these two species in response to bacterial infection could partially result from differences in the innate host response. In response to bacterial infection, white blood cells produce a number of factors that play key roles in the immune response, including nitric oxide (NO). Samples from cultures of bighorn white blood cells were assayed for nitric oxide activity by measurement of an NO end-product, nitrite. Bighorn sheep white blood cells secreted higher levels of NO compared to white blood cells isolated from domestic sheep. A propensity for BHS macrophages to secrete high levels of NO in response to bacterial infection may be a detriment to host survival

Technical Abstract: Bighorn sheep (Ovis canadensis) are more susceptible to certain bacterial infections than are domestic sheep (Ovis aries). We hypothesized that the variability between these two ovine species in response to bacterial challenge could partially result from differences in the host inflammatory response elicited. In response to bacterial challenge, macrophages produce a number of molecules that play key roles in the inflammatory response, including highly reactive nitrogen intermediates such as nitric oxide (NO). Nitric oxide is a regulatory component of signal transduction cascades and may have cytostatic or cytotoxic effects during inflammatory responses. Supernatants from LPS-stimulated macrophage cultures were assayed for nitric oxide activity via measurement of the NO metabolite, nitrite. Bighorn sheep macrophages secreted higher basal levels of NO compared to macrophages isolated from domestic sheep. Moreover, in response to LPS stimulation, BHS macrophagaes secreted significantly higher levels of NO. In contrast, levels of NO secreted by domestic sheep macrophages in response to LPS did not differ from levels in non-stimulated cultures. The addition of an inducible nitric oxide synthase (iNOS) inhibitor, N**G-monomethyl-L-arginine, to stimulated cultures reduced the levels of nitrite in supernatants to levels similar to those observed in non-stimulated cultures. The role of NO in pathogenesis is complex, having been shown to be important in the clearance of pathogens, but responsible for the pathophysiology seen in many diseases. Thus, the species-specific differences in NO production in response to LPS stimulation observed in the present study may partially explain between species variance in host response to bacterial infection.