, Volume 28, Issue 3-4, pp 256-263

In vitro effects of leukotriene B4 (LTB4) on canine PMN effector function(s)

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The canine has become an accepted research model for the examination of a number of human clinical conditions. Despite it's status as a research model, little is known regarding the peripheral effects of inflammatory mediator substances. Products of arachidonic acid metabolism (leukotrienes) are reported capable of altering leukocyte functions. Because of the emerging importance of the canine research model and leukotrienes we examined the effects of leukotriene B4 (LTB4) on severalin vitro functions of isolated canine peripheral polymorphonuclear leukocytes (PMN). Changes in forward angle light scatter properties of the cells were used as one measure of PMN activation. Other functional changes examined following LTB4 pretreatment included chemotactic capability, the electrophysiological state of the cell plasma membrane, and the metabolic oxidative response (i. e. H2O2 production). Random cellular movement of PMNs increased by 120% and 72% following preincubation with 10−7 and 10−9 M LTB4, respectively. LTB4 between 10−7 and 10−13 M did not significantly alter cellular resting membrane potential. Between 10−7 and 10−9 M LTB4 elicited significant levels of cellular H2O2 production. Although significant, H2O2 production was <40% that induced by phorbol myristate acetate (PMA). In numerous respects, caninein vitro PMN responses parallel previous reports of human cell function(s) in the presence of inflammatory mediators and may represent an attractive alternative for investigation of PMN dysfunctions.

Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under work units B 2082 and B2152. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should by the Defense Nuclear Agency has been given or should be inferred. Research was conducted according to the principles enunciated in the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources, National Research Council.