Journal of lipid mediators 

About: Journal of lipid mediators is an academic journal. The journal publishes majorly in the area(s): Platelet-activating factor & Receptor. It has an ISSN identifier of 0921-8319. Over the lifetime, 264 publications have been published receiving 3717 citations.

Extracellular phospholipase A2 expression and inflammation: the relationship with associated disease states

Abstract: Human non-pancreatic PLA2 has been the object of intense scrutiny for a relatively short period of time. Its role in physiology remains enigmatic. While PLA2 may serve to remodel or remove peroxidised or senescent phospholipids, the enormous magnitude of its upregulation during infectious or inflammatory episodes is consistent with a role in host defense. However, the nature of this role remains elusive. Attempts to relegate this enzyme to the genre of acute phase reactants have not been helpful in unravelling its role. Difficulty in obtaining adequate amounts of native snp-PLA2 prior to the availability of recombinant snp-PLA2 led to the widespread use of snake venom homologs, particularly in studies of the biology of PLA2. This review has underscored the pitfalls inherent in that approach given the major differences between some venom PLA2s as compared to snp-PLA2. In addition, it bears reiterating that the complex composition of venom allows for potentiation of PLA2 activity by other constituents present in venom. Whether human host defense networks employ this interactive strategy is largely unknown. Nonetheless, in spite of these reservations, some very compelling data have emerged in recent years implicating snp-PLA2 in the initiation or potentiation of local and systemic inflammatory processes. These include sepsis and associated acute lung injury as well as inflammatory arthritides, with rheumatoid arthritis as the prototype. The mechanisms of snp-PLA2 homeostasis are considerably better understood, and it has become apparent that snp-PLA2 is an integral part of a larger network of proinflammatory cytokines, growth factors and lipid mediators. The interrelationship between the functions of secretory and cytosolic PLA2s remains to be defined. A number of selective PLA2 inhibitors have been identified which will allow for discrimination between the actions of these classes of PLA2. The availability of synthetic inhibitors in conjunction with endogenous modulators of PLA2s will shift the biology of PLA2 from the realm of the inferential to that of the mechanistic.

Specific receptors of platelet-activating factor, receptor heterogeneity, and signal transduction mechanisms.

Abstract: Platelet-activating factor (PAF) exerts its actions through the activation of specific PAF receptors found in a variety of cells and tissues. The signal transduction process induced by PAF appears to be modulated by guanine nucleotide-regulatory proteins (G-proteins) in both rabbit and human platelets and also in human polymorphonuclear leukocytes (PMNs). The PAF receptor, the G-protein coupled to the receptor, and the signal transduction mechanisms in human platelets are different from those in human PMNs. The PAF receptor in human PMNs may also be different from that in human eosinophils. The existence of receptor heterogeneity in guinea pig eosinophils is also proposed. Thus PAF receptor subtypes do exist. Further investigations are required to understand the role of each individual PAF receptor subtype.

Marked overproduction of non-cyclooxygenase derived prostanoids (F2-isoprostanes) in the hepatorenal syndrome.

Abstract: In spite of extensive searching for clues to the pathogenesis of the hepatorenal syndrome (HRS), its cause remains an enigma. The renal dysfunction in HRS has been attributed to intense but reversible renal vasoconstriction. This has engendered the hypothesis that the renal vasoconstriction is caused by a circulating factor. Patients with HRS exhibit chronic endotoxemia and may have tissue hypoxia, an environment conducive for the formation of free radicals. Recently, we discovered a series of novel prostaglandin (PG) F2-like compounds, termed F2-isoprostanes, that are produced in vivo as products of free radical catalyzed lipid peroxidation independent of the cyclooxygenase enzyme. One of these compounds, 8-epi-PGF2 alpha, has been found to be an extremely potent renal vasoconstrictor. Therefore, we quantified levels of these prostanoids in patients with HRS and compared them to various control groups. Plasma levels of these compounds were markedly elevated only in patients with HRS (113 +/- 30 pg/ml) (p < 0.01) compared to normal controls (19 +/- 7 pg/ml), patients with compensated liver disease (20 +/- 4 pg/ml), patients with decompensated liver disease (22 +/- 4 pg/ml), and patients with chronic renal failure (23 +/- 4 pg/ml). The increased levels of these compounds are unlikely the result of reduced hepatic and renal clearance of the compounds since levels are not markedly increased in patients with either decompensated liver disease or chronic renal failure alone. Whether F2-isoprostanes are the elusive mediators responsible for the renal vasoconstriction in HRS remains to be established. However, these findings do suggest that oxidant injury may be a fundamental abnormality involved in the pathogenesis of HRS.

PAF/cytokine Auto-Generated Feedback Networks in Microvascular Immune Injury: Consequences in Shock, Ischemia and Graft Rejection

Abstract: The catastrophe theory evolved by Thom and Zeeman proposes a mathematical definition for the abrupt or 'catastrophic' changes that can suddenly occur in normally well-ordered and smooth-running systems. We have integrated this theory with our own PAF/cytokine feedback network hypothesis to explain the control and dysfunction of the inflammatory response. This process involves the activation of cells and factors such as proteases, and is coordinated by mediators such as PAF, cytokines and growth factors, minute amounts of which can prime cells to respond in an enhanced manner to subsequent agonistic stimuli. PAF and certain cytokines also possess the unique property of being able to induce the release of each other and their own generation in vivo. This 'singularity' may enable a self-generating feedback network to become established. The priming ability of these mediators indicates the extreme sensitivity of the inflammatory process and importance of a homeostatic equilibrium between the vectors involved in the priming and feedback processes and internal suppressive mechanisms. In pathological conditions, one can consider the phenomenon of PAF and cytokine autogeneration as a 'fold' in the feedback network and an expression of the singularity characteristic of the catastrophe hypothesis. This may lead to systemic toxicity and microcirculatory collapse, a characteristic feature of shock, sepsis, asthma, ischemia and graft rejection. A combination of drugs antagonizing the various feedback components may inhibit this catastrophic process and thus provide more successful therapy of these conditions.

Pheromonal and reproductive function of F prostaglandins and their metabolites in teleost fish

Abstract: Although the function of prostaglandins in fish reproduction has not been well studied, it is becoming increasingly clear that prostaglandin F2 alpha or a compound closely resembling it serves three critical roles mediating reproductive activities in teleost fish. First, it appears to play a paracrine role in the ovary stimulating and/or modulating follicular rupture. Second, circulating levels of F prostaglandins rise at the time of ovulation and travel to the brain where they elicit female sexual behavior. Third, recent studies indicate that F prostaglandin is metabolized and released to the water where it functions as a sex pheromone stimulating male sexual behavior. Although these roles have been best characterized in the goldfish, ongoing studies indicate that metabolites of prostaglandin F2 alpha may commonly function as pheromones in many fish. Many questions remain about the identity(ies), origins, and species-specificity of the prostaglandin pheromone.