The polymorphonuclear leukocyte (PMN) plays an integral role in the development of permeability pulmonary edema associated with the adult respiratory distress syndrome (ARDS). This report describes 3 patients with ARDS secondary to systemic sepsis who demonstrated an abnormal diffuse accumulation of Indium (111In)-labeled PMNs in their lungs, without concomitant clinical or laboratory evidence of a primary chest infection. In one patient, the accumulation of the pulmonary activity during an initial pass suggested that this observation was related to diffuse leukoaggregation within the pulmonary microvasculature. A 4th patient with ARDS was on high-dose corticosteroids at the time of a similar study, and showed no pulmonary accumulation of PMNs, suggesting a possible reason for the reported beneficial effect of corticosteroids in human ARDS.
"Acute respiratory distress syndrome (ARDS) is a lifethreatening , hyperacute inflammatory response that occurs in the lungs following trauma or sepsis. Inflammatory cell activation, and in particular neutrophil activation, has been implicated in the early stages of ARDS pathogenesis (Powe et al. 1982, Donnelly et al. 1994a,b, Chollet-Martin et al. 1996). MIF has been demonstrated to play a key role in acute lung injury (Donnelly et al. 1997), highlighted by its ability to accentuate pro-inflammatory cytokine production in ex vivo alveolar cells derived from patients with ARDS. "
[Show abstract][Hide abstract] ABSTRACT: The diverse actions of macrophage migration inhibitory factor (MIF) within the immuno-neuroendocrine system are yet to be fully understood, but it is clear that MIF plays a pivotal role in the regulation of both the innate and adaptive immune response. An emerging body of data presently indicates that MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control the 'set point' and magnitude of the immune and inflammatory response. In this article we will review the actions of MIF within the immune system and discuss the overlapping and contrasting aspects of MIF and glucocorticoid biology. In particular we will focus on the role of MIF within the immuno-neuroendocrine interface and suggest molecular mechanisms by which MIF may counter-regulate glucocorticoid function. Finally we will discuss emerging evidence that functional MIF gene-promoter polymorphisms render one susceptible to elevated MIF expression, and the development of an exaggerated immune/inflammatory response that potentiates the progression to chronic inflammatory disease.
Journal of Endocrinology 11/2003; 179(1):15-23. DOI:10.1677/joe.0.1790015 · 3.72 Impact Factor
"The essence of adult respiratory distress syndrome (ARDS) is thought to be an increase in permeability of pulmonary vessels resulting in edema. In lung injury, the localized aggregation of polymorphonuclear cells (PMNs) within the pulmonary microvasuculature is an important prerequisite (Powe 1982). In- Received February 28, 1995; revision accepted for publication September 15, H. Kubo et al. creased PMN adhesiveness to endothelial cells is a critical, early step in the sequence of events leading to PMN-mediated injury. "
[Show abstract][Hide abstract] ABSTRACT: We investigated the mechanisms of increase in the pulmonary vascular permeability, focusing on the changes in the peripheral white blood cell (WBC) counts and the surface expression of CD18 on polymorphonuclear cells (PMNs). Anesthetized sheep with chronic lung lymph fistulas were used in this study. We infused synthetic endotoxin (LPS) at a rate of 10 ng/kg/min (i.v.) continuously for 24 hr. We measured lung lymph flow, lymph-to-plasma protein concentration ratio and WBC counts in blood and lung lymph, and the PMNs' surface expression of CD18 before and at 2, 10 and 24 hr after the start of endotoxin infusion, respectively. CD18 was analyzed by flow cytometry using monoclonal anti-CD18 antibody. We found that the pulmonary vascular permeability increased during 2-4 hr after the start of endotoxin infusion, and returned to the baseline over 10 hr. At time 2 hr period, the number of WBCs in the lung lymph increased, the number of peripheral WBCs, mostly PMNs, decreased and the surface expression of CD18 on the peripheral PMNs was up-regulated. At time 10 and 24 hr, the number of WBCs in lung lymph decreased, the number of peripheral WBCs increased and CD18 expression was down-regulated. These data indicate that up-regulation of CD18 expression promotes the PMN adherence to the pulmonary endothelium, migration into the lung and increases the pulmonary vascular permeability. We conclude that the continuous endotoxin infusion up-regulates CD18, which contributes to the PMN migration into the lung.
The Tohoku Journal of Experimental Medicine 12/1995; 177(3):213-22. DOI:10.1620/tjem.177.213 · 1.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zymosan activated plasma infusion induces pulmonary sequestration of neutrophils and the release of TXA2 into the pulmonary vascular bed causing profound and transient pulmonary hypertension.Since ethanol (ETOH) inhibits several inflammatory functions of neutrophils, including adherence and aggregation, we examined the ability of anesthetic doses of ETOH to alter the hemodynamic and cellular response to the infusion of zymosan activated plasma (ZAP) in vivo. Twenty five ml of autologous ZAP was intravenously infused into five control and seven (ETOH-treated sheep during mechanical ventillation. In control sheep the mean pulmonary artery pressure (PAP) transiently increased from 14.7±1.4 mm Hg (mean±SEM) to a pead of 38+8 mm Hg by three minutes after beginning the infusion of ZAP. Blood leukocyte concentration transiently decreased 19% below the baseline value due to pulmonary sequestration of polymorphonuclear leukocytes (PMN). Plasma TXB2 levels measured by radioimmunoassay (RIA) increased from 0.2 to 5.4 ng/ml six minutes after the initiation of ZAP infusion.In five sheep, intravenous infusion of 200 ml of 96% ETOH yielded very high plasma concentrations (882±101 mg%) and completely inhibited both the rise of PAP and the increase of plasma TXB2 levels after ZAP infusion. However, blood leukocytes transiently decreased 58% below the baseline value. Lower plasma levels of ETOH (200 and 400 mg%) did not prevent either the increase of PAP or the elevation of plasma TXB2 after ZAP infusion.
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