Chest
Today’s Practice of Cardiopulmonary MedicineRole of Humoral Mediators in Adult Respiratory Distress Syndrome
Section snippets
SEROTONIN (5-HYDROXYTRYPTAMINE, 5-HT)
This vasoactive amine has the capacity to cause pulmonary arterial constriction, as well as generalized bronchospasm, including peripheral bronchioles. The highest concentrations of serotonin outside of the intestine are contained in the dense bodies of platelets. Platelet entrapment, activation, and release in the lungs is therefore likely to result in high local concentrations of serotonin. The effects on pulmonary function can be significant; for example, after experimental pulmonary
PLATELET ACTIVATING FACTOR
Platelet entrapment in the lungs after pulmonary embolization is likely due to the interaction of circulating platelets with thrombin in the clot. A number of other clinical and experimental states are associated with platelet sequestration; however, the mechanism of these platelet interactions are often obscure.
Platelet activating factor, a recently described and synthesized glycerol phosphorylcholine, may play an important role in platelet activation. Platelet activating factor is synthesized
LEUKOCYTES
Agreement is general that leukocytes and their products are principal mediators of the adult respiratory distress syndrome. These inflammatory cells may be entrapped in the lungs in large numbers.14 Their importance is inferred from their strategic histologic location in proximity to damaged lung.15 Furthermore, experimental depletion of WBCs protects animals from developing high protein pulmonary edema following challenge with agents such as activated complement16 or endotoxin.17 Similar
CHEMOTAXIS
Events which initiate the adult respiratory distress syndrome are thought to involve the generation of chemoattractants which cause WBCs to localize in the lungs. The lungs produce several types of chemoattractants. Platelet activating factor occupies a central role, both acting as a chemoattractant5 and stimulating synthesis of others. Thus, mast cells can be triggered by platelet activating factor to produce the lipoxygenase derivatives, hydroxyeicosatetraenoic acid and leukotriene B4.24 Mast
TOXIC WBC PRODUCTS
A number of recent studies describe several potent products of neutrophils which could cause reversible, as well as permanent, tissue injury and altered hemodynamics. These toxic WBC agents are useful in normal, contained bactericidal processes. Their importance is illustrated by the susceptibility of patients to recurrent infections who have genetic defects in WBC production of oxygen radicals (chronic granulomatous disease) or in the production and release of granular enzymes from WBCs;
OXYGENATION PRODUCTS OF ARACHIDONIC ACID
The salutary effects of antioxidants may not only be due to their scavaging of toxic free radicals, but may also relate to their possible inhibition of arachidonic acid metabolism. Initial steps in the oxygenation of arachidonic acid involves cyclooxygenation and lipoxygenation leading to the generation of peroxy radicals.31 Antioxidants may modify this step and reduce synthesis of agents that may play important roles in the adult respiratory distress syndrome such as leukotriene and
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Cited by (14)
Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells
2008, Analytical BiochemistryCitation Excerpt :TxA2, another prostanoid, has been described as being important in megakaryocytic-derived cells [28]. It is a biologically active compound that plays a major role in hemostasis, thrombosis, and several other diseases such as adult respiratory distress syndrome [29]. TxS converts PGH2 to TxA2, which is immediately converted to TxB2 by a nonenzymatic reaction, with TxB2 being the only measured compound.
Acute Respiratory Failure
2008, Critical Care Medicine: Principles of Diagnosis and Management in the AdultResuscitation
1990, InjuryMechanisms of acute lung injury. What have we learned from experimental animal models?
1986, Critical Care Clinics
Supported in part by the National Institutes of Health grants GM24891-06 and HL16714-08, by the US Navy Office of Naval Research contract N00014-79-C-0168, by the Brigham Surgical Group, Inc., and by the Trauma Research Foundation.