The Role of Eicosanoids in the Chemotactic Response to Pasteurella haemolytica Infection

Abstract

The chemotactic role of eicosanoids in the pathogenesis of Pasteurella haemolytica infection was studied, using a tissue chamber infection model and pharmacological inhibitors of eicosanoid synthesis. Tissue chambers were implanted subcutaneously in 12 calves allotted to three treatment groups of equal size. At 45 days after implantation, calves received saline, dexamethasone, or phenylbutazone treatments, and tissue chambers in all animals were then inoculated with P.haemolytica. Chamber fluid samples were collected before inoculation and at 2, 6, 18, 40, and 90 h after inoculation. Bacterial counts, total leukocyte counts, pH and albumin concentrations in chamber fluids were determined using standard bacteriological and clinical pathological methods. Concentrations of eicosanoids and activity of interleukin-1 (IL-1) were measured by radioimmunoassay and a helper T cell bioassay, respectively. Concentrations of leukotriene B, (LTB,), thromboxane Bz (TXBz), 6-keto-prostaglandin Flm (PGF,,) and prostaglandin Ez (PGEJ increased markedly after inoculation. An inhibitory effect of dexamethasone on both LTB, production and neutrophil influx, together with the temporal relationship between these two events, suggested that LTB, served as a chemo-attractant. Activity-time profiles for IL-1 in chamber fluids were similar to those of the eicosanoids. Phenylbutazone and dexamethasone reduced the severity of the inflammatory responses as measured by lower concentrations of albumin and higher p H in treated versus control chamber fluids. The results of this study suggest that eicosanoid inflammatory mediators play an important chemotactic role in the pathogenesis of P. haemolytica infection.

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

“…4) as important chemotactic agents for bovine neutrophils and mediators of inflammation in M. haemolytica infection [28,57,68,176]. LTB4 and 5-HETE may in fact serve as biological amplifiers in the inflammatory process by inducing a further accumulation of polymorphonuclear leukocytes (PMN) at the site of injury [69,120].…”

A prioriprobabilities of separable quantum states

“…[19,20]). ) Clarke and Barron [21,22] (cf. [23]) have established that Jeffreys' priors (the normalized volume elements of Fisher information metrics) asymptotically maximize Shannon's mutual information between a sample of size n and the parameter, and that Jeffreys' prior is the unique continuous prior that achieves the asymptotic minimax risk when the loss function is the Kullback-Leibler distance between the true density and the predictive density.…”

Mannheimia haemolyticaleukotoxin-induced increase in leukotriene B4production by bovine neutrophils is mediated by a sustained and excessive increase in intracellular calcium concentration

“…However, changes in [Ca 2+ ] i also constitute a common signal transduction mechanism involved in host defense responses that serve to protect animals against bacterial infection. Therefore, the overall goal of the present study was to explain why LKT‐induced increase in [Ca 2+ ] i causes production of large amounts of LTB 4 , which has been implicated in the excessive inflammation and failure in host defenses involved in M. haemolytica infection [5]. Considering that normal physiological responses involving Ca 2+ as a second messenger usually involve transient increases in [Ca 2+ ] i [12–16], the hypothesis developed to explain the role of [Ca 2+ ] i in the pathogenic responses of neutrophils to M. haemolytica infection is that LKT activates neutrophils by causing a sustained and excessive increase in [Ca 2+ ] i , which results in uncontrolled synthesis of inflammatory mediators.…”