Eicosanoids act in nodulation reactions to bacterial infections in newly emerged adult honey bees, Apis mellifera, but not in older foragers

Nodulation is the first, and qualitatively predominant, cellular defense reaction to bacterial infections in insects. We tested the hypothesis that eicosanoids also mediate nodulation reactions to bacterial challenge in adults of a social insect, the honey bee, Apis mellifera. Treating newly-emerged experimental bees with the eicosanoid biosynthesis inhibitor, dexamethasone, impaired nodulation reactions to bacterial infections, and the influence of dexamethasone was reversed by treating infected insects with arachidonic acid, an eicosanoid precursor. Several other eicosanoid biosynthesis inhibitors, including the cyclooxygenase inhibitor, indomethacin, and the dual cyclooxygenase/lipoxygenase inhibitor, phenidone, also impaired the ability of experimental honeybees to form nodules in reaction to bacterial challenge. The influence of phenidone on nodulation was expressed in a dose-dependent manner. However, in experiments with older honey bees foragers, similar bacterial challenge did not evoke nodulation reactions. We infer from our results that while eicosanoids mediate cellular immune responses to bacterial infections in newly emerged honey bees, and more broadly, in most insect species, nodulation reactions to bacterial challenge probably do not occur in all phases of insect life cycles.     

Eicosanoids mediate melanotic nodulation reactions to viral infection in larvae of the parasitic wasp, Pimpla turionellae

Nodulation is the quantitatively predominant insect cellular immune function activated in response to bacterial, fungal and some viral infections. We posed the hypothesis that parasitoid insects express melanotic nodulation reactions to viral challenge and that eicosanoids mediate these reactions. Treating fifth-instar larvae of the ichneumonid endoparasitoid Pimpla turionellae with Bovine Herpes Simplex Virus-1 (BHSV-1) induced nodulation reactions in a challenge dose-dependent manner. Experimental larvae treated with the cyclooxygenase inhibitor, indomethacin, the lipoxygenase inhibitor, esculetin, and the phospholipase A2 inhibitor, dexamethasone, resulted in severely impaired nodulation reactions to our standard BHSV-1 challenge dose. The immunoinhibitory influence of dexamethasone was reversed in larvae reared on culture medium amended with arachidonic acid, the fatty acid precursor of eicosanoid biosynthesis. Larvae that had been reared on media amended with indomethacin, esculetin, or dexamethasone were also compromised in their nodulation reactions to viral challenge. The influence of the orally administered pharmaceutical was expressed in a dose-dependent manner. Finally, wasp larvae reared in the presence of indomethacin and dexamethasone expressed significantly decreased levels of phenoloxidase activity in response to viral challenge. These findings draw attention to the idea that endoparasitoid insects express cellular immune reactions to viral challenge; they also support our hypothesis that eicosanoids mediate nodulation reactions to viral challenge in these highly specialized insects.     

Eicosanoid Signaling in Insects: from Discovery to Plant Protection

Prostaglandins (PGs) and related eicosanoids are signal moieties derived from arachidonic acid and two other C20 polyunsaturated fatty acids. They were discovered in the 1930s in the context of mammalian reproductive physiology; PGs were associated with the prostate gland, hence their name, and they stimulate uterine smooth muscle contraction. Determining PG chemical structures in the early 1960s and demonstrating that they mediate many human pathophysiological events in the 1970s stimulated intensive research over the following decades in universities, governments and the private sector. Interest in the biological significance of PGs in insects arose in the 1970s and 1980s, which opened a new research frontier. PGs act in reproduction, releasing egg-laying behaviors in some species and signaling egg-maturation events in the Drosophila and silk moth models. They act in insect immunity, mediating and coordinating cellular and humoral responses to wounds, infection and invasion. PGs act in ion transport physiology in insect Malpighian tubules and recta. These compounds also mediate physiological trade-offs between insect immunity and reproduction. Finally, they are central players in the molecular ecology of interactions between blood-feeding insects and their vertebrate hosts. Some PG functions are critical at specific, crucial moments in insect lives, moments we consider ‘emergencies,’ such as the immediate reactions to infection. Certain microbial species have keyed into insect PG signaling and they evolved mechanisms to disable insect immune reactions to infection by inhibiting key enzymes in PG biosynthesis. We provide proof-of-principle that RNA interference treatments designed to silence genes in PG signaling disrupts insect immunity. In this review we describe the history, chemistry and biology of PGs. We use this background to argue that because PGs and other eicosanoids act in emergency situations, they are visible targets for development and deployment of novel insect pest management technologies.     

Eicosanoids mediate nodulation reactions to a mollicute bacterium in larvae of the blowfly, Chrysomya megacephala

Nodulation is the temporally and quantitatively most important cellular defense response to bacterial, fungal and some viral infections in insects. We tested the hypothesis that prostaglandins and other eicosanoids are responsible for mediating nodulation reactions to bacterial infection in larvae of the blowfly Chrysomya megacephala. Third-instar larvae treated with Ureaplasma urealyticum formed nodules in a challenge dose-dependent manner. Nodulation was evoked shortly after injection and reached a maximum of approximately 25 nodules/larva within 8 h. Larvae treated with the glucocorticoid, dexamethasone and the cyclooxygenase inhibitors, indomethacin and piroxicam were impaired in their ability to form nodules following U. urealyticum infection. The number of nodules decreased with increasing doses of piroxicam. Contrarily, treating larvae with the lipooxygenase inhibitor, esculetin, and the dual cyclooxygenase/lipooxygenase inhibitor, phenidone did not influence nodulation reactions to infection. Supplying dexamethasone-treated larvae with the eicosanoid precursor, arachidonic acid, reversed the inhibitory effect of dexamethasone on nodulation. We infer from these results that eicosanoids mediate nodulation reactions to infection of a bacterial species that lacks cell walls in larvae of the blowfly, C. megacephala.     

Modulation by eicosanoid biosynthesis inhibitors of immune responses by the insect Manduca sexta to the pathogenic fungus Metarhizium anisopliae

Metarhizium anisopliae conidia (spores) reduced weight gain and caused death when injected into Manduca sexta larvae. When the fungus was co-injected with the eicosanoid biosynthesis inhibitor dexamethasone, larval weight gain was further reduced and mortality increased. These effects were reversed when dexamethasone was given together with the eicosanoid precursor arachidonic acid (AA). Similarly, treatment with other eicosanoid biosynthesis inhibitors (esculetin, phenidone, ibuprofen, and indomethacin) with differing modes of action enhanced the reduction in weight gain caused by mycosis. Injection of M. anisopliae conidia induced nodule formation in vivo; nodule numbers were reduced by dexamethasone, and restored by AA. Incubation of hemocytes with conidia caused microaggregation of hemocytes (indicative of nodule formation) in vitro and this was inhibited by dexamethasone, suggesting that dexamethasone acts directly on hemocytes, although inhibition was only partially reversed by AA. We suggest that the M. sexta immune response to fungal pathogens is normally modulated by physiological systems that include eicosanoid biosynthesis. This is the first demonstration that the virulence of a fungal entomopathogen can be enhanced by compromising the insect host's immune system.     

Eicosanoids mediate insect hemocyte migration

Hemocyte migration toward infection and wound sites is an essential component of insect defense reactions, although the biochemical signal mechanisms responsible for mediating migration in insect cells are not well understood. Here we report on the outcomes of experiments designed to test the hypotheses that (1) insect hemocytes are able to detect and migrate toward a source of N-formyl-Met-Leu-Phe (fMLP), the major chemotactic peptide from Escherichia coli and (2) that pharmaceutical modulation of eicosanoid biosynthesis inhibits hemocyte migration. We used primary hemocyte cultures prepared from fifth-instar tobacco hornworms, Manduca sexta in Boyden chambers to assess hemocyte migration toward buffer (negative control) and toward buffer amended with fMLP (positive control). Approximately 42% of negative control hemocytes migrated toward buffer and about 64% of positive control hemocytes migrated toward fMLP. Hemocyte migration was inhibited (by >40%) by treating hornworms with pharmaceutical modulators of cycloxygenase (COX), lipoxygenase and phospholipase A2 (PLA2) before preparing primary hemocyte cultures. The influence of the COX inhibitor, indomethacin, and the glucocorticoid, dexamethasone, which leads to inhibition of PLA2, was expressed in a dose-dependent way. The influence of dexamethasone was reversed by injecting arachidonic acid (precursor to eicosanoid biosynthesis) into hornworms before preparing primary hemocyte cultures. The saturated fatty acid, palmitic acid, did not reverse the inhibitor effect. These findings support both our hypotheses, first that insect hemocytes can detect and respond to fMLP, and second, that insect hemocyte migration is mediated by eicosanoids.     

Lipopolysaccharide evokes microaggregation reactions in hemocytes isolated from tobacco hornworms, Manduca sexta

Insect cellular immune reactions to bacterial infection include nodule formation. Eicosanoids mediate several cellular actions in the nodulation process, including formation of hemocyte microaggregates, an early step. In previous work, we reported that isolated hemocytes produce and secrete eicosanoids that influence hemocyte behavior in response to bacterial challenge. We also reported that microaggregate formation in response to challenge was mediated by prostaglandins (PGs), but not by products of the lipoxygenase (LOX) pathways. In this paper we describe experiments designed to test the idea that exposing isolated hemocytes to lipopolysaccharide (LPS) evokes formation of hemocyte microaggregates and this cellular action is mediated by PGs. Results show that isolated hemocyte preparations challenged with LPS formed more hemocyte microaggregates than unchallenged preparations (6.9x10(3) microaggregates/ml hemolymph vs. 2.5x10(3) microaggregates/ml hemolymph). LPS challenge stimulated formation of hemocyte microaggregates in a dose dependent manner. Experimental groups pretreated with cyclooxygenase inhibitors produced fewer hemocyte microaggregates in response to LPS challenge than untreated control groups. The formation of hemocyte microaggregates was not influenced by LOX inhibitors. Furthermore, the influence of dexamethasone was reversed by supplementing the experimental groups with the eicosanoid precursor fatty acid molecule, arachidonic acid and PGH(2). Palmitic acid, which is not substrate for eicosanoid biosynthesis, did not reverse the effects of dexamethasone on the formation of microaggregates. The LOX product 5(S)hydroperoxyeicosa-6E,8Z,11Z,14Z-tetraenoic acid also did not reverse the effects of dexamethasone. These results are consistent with similar investigations performed with bacterial suspensions. We infer that isolated hemocyte preparations recognize and react to LPS by forming microaggregates and this reaction is mediated by PGs, but not products of the LOX pathway.     

The complex role of eicosanoids in the brain: Implications for brain tumor development and therapeutic opportunities

Eicosanoids are a family of bioactive lipids that play diverse roles in the normal physiology of the brain, including neuronal signaling, synaptic plasticity, and regulation of cerebral blood flow. In the brain, eicosanoids are primarily derived from arachidonic acid, which is released from membrane phospholipids in response to various stimuli. Prostaglandins (PGs) and leukotrienes (LTs) are the major classes of eicosanoids produced in the brain, and they act through specific receptors to modulate various physiological and pathological processes. Dysregulation of eicosanoids has been implicated in the development and progression of brain tumors, including glioblastoma (GBM), meningioma, and medulloblastoma. Eicosanoids have been shown to promote tumor cell proliferation, migration, invasion, angiogenesis, and resistance to therapy. Particularly, PGE2 promotes GBM cell survival and resistance to chemotherapy. Understanding the role of eicosanoids in brain tumors can inform the development of diagnostic and prognostic biomarkers, as well as therapeutic strategies that target eicosanoid pathways. Cyclooxygenase (COX)-2 and 5-lipoxygenase (LOX) inhibitors have been shown to reduce the growth and invasiveness of GBM cells. Moreover, eicosanoids have immunomodulatory effects that can impact the immune response to brain tumors. Understanding the role of eicosanoids in the immune response to brain tumors can inform the development of immunotherapy approaches for these tumors. Overall, the complex role of eicosanoids in the brain underscores the importance of further research to elucidate their functions in normal physiology and disease, and highlights the potential for developing novel therapeutic approaches that target eicosanoid pathways in brain tumors.     

Eicosanoids up-regulate production of reactive oxygen species by NADPH-dependent oxidase in Spodoptera exigua phagocytic hemocytes

Eicosanoids mediate cellular immune responses in insects, including phagocytosis of invading microbes. Phagocytosis entails two major steps, the internalization of microbes and the subsequent killing of them via formation of reactive oxygen species (ROS). Here, we posed the hypothesis that eicosanoids mediate ROS production by activating NADPH-dependent oxidase (NOX) and tested the idea in the model insect, Spodoptera exigua. A NOX gene (we named SeNOX4) was identified and cloned, yielding a full open reading frame encoding 547 amino acid residues with a predicted molecular weight of 63,410 Da and an isoelectric point at 9.28. A transmembrane domain and a large intracellular domain containing NADPH and FAD-binding sites were predicted. Phylogenetic analysis indicated SeNOX4 clusters with other NOX4 genes. SeNOX4 was expressed in all life stages except eggs, and exclusively in hemocytes. Bacterial challenge and, separately, arachidonic acid (AA, a precursor of eicosanoid biosynthesis) injection increased its expression. The internalization step was assessed by counting hemocytes engulfing fluorescence-labeled bacteria. The phagocytic behavior was inhibited by dsRNA suppression of SeNOX4 expression and, separately by dexamethasone (DEX, a specific inhibitor of eicosanoid biosynthesis) treatments. However, injecting AA to dsSeNOX4-treated larvae did not rescue the phagocytic activity. Hemocytic ROS production increased following bacterial challenge, which was sharply reduced in dsSeNOX4-treated, and separately, in DEX-treated larvae. AA partially reversed the suppressed ROS production in dsSeNOX4-treated larvae. Treating larvae with either the ROS-suppressing dsSeNOX4 construct or DEX rendered experimental larvae unable to inhibit bacterial proliferation in their hemocoels. We infer that eicosanoids mediate ROS production during phagocytosis by inducing expression of SeNOX4.     

Eicosanoids influence in vitro elongation of plasmatocytes from the tobacco hornworm, Manduca sexta

Nodule formation is the predominant insect cellular defense reaction to bacterial challenges, responsible for clearing the largest proportion of infecting bacteria from hemolymph circulation. Hemocyte spreading behavior is a critical step in the nodulation process. It has been suggested that eicosanoids mediate several steps in the process. However, the influence of eicosanoids on hemocyte spreading has not been investigated in detail. To test the hypothesis that eicosanoids mediate hemocyte spreading behavior, I treated larvae of the tobacco hornworm, Manduca sexta, with eicosanoid biosynthesis inhibitors and later assessed plasmatocyte elongation on glass slides. Plasmatocytes from larvae treated with dexamethasone did not elongate to the extent of plasmatocytes from untreated control larvae. The dexamethasone effect on plasmatocyte elongation was expressed in a dose-dependent manner and was reversed by injecting dexamethasone-treated larvae with the eicosanoid-precursor fatty acid, arachidonic acid. Palmitic acid, which is not substrate for eicosanoid biosynthesis, did not reverse the influence of dexamethasone on plasmatocyte elongation. Finally, plasmatocytes from larvae treated with a range of eicosanoid biosynthesis inhibitors did not elongate to the extent of plasmatocytes from control larvae. Plasmatocyte width did not appear to be influenced in this study. These findings strongly support the idea that insect plasmatocyte elongation is influenced by eicosanoids.     

Fatty acid composition of fat body and malpighian tubules of the tenebrionid beetle, Zophobas atratus: Significance in eicosanoid-mediated physiology

Total and phospholipid fatty acid composition of fat body and Malpighian tubules from two larval stages, pupae and adults, of Zophobas atratus were analyzed. Saturated and unsaturated C16 and C18 fatty acids were major components and varied by life stage and tissue source. Eicosanoid-precursor fatty acids, including 20:3n-6, 20:4n-6 and 20:5n-3, were present in low quantities and varied by life stage and tissue source. 20:3n-6 was always present in the lowest proportions, indicating that eicosanoids derived from 20:4n-6 and 20:5n-3 (the 2- and 3-series) are likely to be of greater physiological significance in this insect. Fatty acid composition of Z. atratus fat body and Malpighian tubules was independent of diet, suggesting that this insect controls its fatty acid composition to meet the needs of individual tissues and ontogenetic constraints.     

PGE(2) induces oenocytoid cell lysis via a G protein-coupled receptor in the beet armyworm, Spodoptera exigua

Eicosanoids mediate cellular and humoral immune responses in the beet armyworm, Spodoptera exigua, including activation of prophenoloxidase (PPO). PPO activation begins with release of its inactive zymogen, PPO, from oenocytoids in response to prostaglandins (PGs). Based on the biomedical literature, we hypothesized that PGs exert their actions via specific G protein-coupled receptor(s) in S. exigua. This study reports a G protein-coupled receptor (Se-hcPGGPCR1) gene, which is expressed in the hemocytes of S. exigua. The Se-hcPGGPCR1 consists of 420 amino acids and belongs to rhodopsin-type GPCRs. The high content of hydrophobic amino acid residues within the Se-hcPGGPCR1 protein is explained by prediction of seven-transmembrane domains that are characteristic of these GPCRs. Except for the eggs, Se-hcPGGPCR1 was expressed in all life stages. During the larval stage, it was expressed in hemocytes and gut, but not in fat body nor in epidermis. Real time quantitative RT-PCR showed that bacterial challenge induced more than 20-fold increases in its expression level. Fluorescence in situ hybridization showed that Se-hcPGGPCR1 was expressed in a specific hemocyte type, the oenocytoids. A specific eicosanoid, PGE₂, significantly induced oenocytoid lysis and increased PO activity in the plasma. In contrast, when Se-hcPGGPCR1 expression was suppressed by RNA interference (RNAi), the oenocytoid lysis and the PO activation in response to PGE₂ were not elevated above basal levels. A binding assay using intracellular calcium mobilization showed that the RNAi-treated hemocytes were significantly less responsive to PGE₂ than the control hemocytes. These results support our hypothesis with the specific finding that PGE₂ acts through Se-hcPGGPCR1 to activate PPO by lysing oenocytoids.     

Anopheles gambiae eicosanoids modulate Plasmodium berghei survival from oocyst to salivary gland invasion

Eicosanoids affect the immunity of several pathogen/insect models, but their role on the Anopheles gambiae response to Plasmodium is still unknown. Plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (IN), or a substrate, arachidonic acid (AA), at day 7 or day 12 post-infection (p.i.). Salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. IN promoted infection upon sporozoite release from oocysts, but inhibited infection when sporozoites were still maturing within the oocysts, as observed by a reduction in the number of sporozoites reaching the salivary glands. AA treatment had the opposite effect. We show for the first time that An. gambiae can modulate parasite survival through eicosanoids by exerting an antagonistic or agonistic effect on the parasite, depending on its stage of development.     

Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology

Eicosanoids have been implicated in a vast number of devastating inflammatory conditions, including arthritis, atherosclerosis, pain, and cancer. Currently, over a hundred different eicosanoids have been identified, with many having potent bioactive signaling capacity. These lipid metabolites are synthesized de novo by at least 50 unique enzymes, many of which have been cloned and characterized. Due to the extensive characterization of eicosanoid biosynthetic pathways, this field provides a unique framework for integrating genomics, proteomics, and metabolomics toward the investigation of disease pathology. To facilitate a concerted systems biology approach, this review outlines the proteins implicated in eicosanoid biosynthesis and signaling in human, mouse, and rat. Applications of the extensive genomic and lipidomic research to date illustrate the questions in eicosanoid signaling that could be uniquely addressed by a thorough analysis of the entire eicosanoid proteome.     

Genes encoding phospholipases A2 mediate insect nodulation reactions to bacterial challenge

We propose that expression of four genes encoding secretory phospholipases A₂ (sPLA₂) mediates insect nodulation responses to bacterial infection. Nodulation is the quantitatively predominant cellular defense reaction to bacterial infection. This reaction is mediated by eicosanoids, the biosynthesis of which depends on PLA₂-catalyzed hydrolysis of arachidonic acid (AA) from cellular phospholipids. Injecting late instar larvae of the red flour beetle, Tribolium castaneum, with the bacterium, Escherichia coli, stimulated nodulation reactions and sPLA₂ activity in time- and dose-related manners. Nodulation was inhibited by pharmaceutical inhibitors of enzymes involved in eicosanoid biosynthesis, and the inhibition was rescued by AA. We cloned five genes encoding sPLA₂ and expressed them in E. coli cells to demonstrate these genes encode catalytically active sPLA₂s. The recombinant sPLA₂s were inhibited by sPLA₂ inhibitors. Injecting larvae with double-stranded RNAs specific to each of the five genes led to reduced expression of the corresponding sPLA₂ genes and to reduced nodulation reactions to bacterial infections for four of the five genes. The reduced nodulation was rescued by AA, indicating that expression of four genes encoding sPLA₂s mediates nodulation reactions. A polyclonal antibody that reacted with all five sPLA₂s showed the presence of the sPLA₂ enzymes in hemocytes and revealed that the enzymes were more closely associated with hemocyte plasma membranes following infection. Identifying specific sPLA₂ genes that mediate nodulation reactions strongly supports our hypothesis that sPLA₂s are central enzymes in insect cellular immune reactions.     

Arachidonate-derived dihomoprostaglandin production observed in endotoxin-stimulated macrophage-like cells

Eicosanoids, including the prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids, epoxyeicosatetraenoic acids, and related compounds, are biosynthetic, bioactive mediators derived from arachidonic acid (AA), a 20:4(n-6) fatty acid. We have developed a comprehensive and sensitive mass spectral analysis to survey eicosanoid release from endotoxin-stimulated RAW 264.7 macrophage-like cells that is capable of detecting over 70 diverse eicosanoids and eicosanoid metabolites, should they be present. We now address the question: Are biologically significant eicosanoids being overlooked? Herein, we illustrate a general approach to diverse isotope metabolic profiling of labeled exogenous substrates using mass spectrometry (DIMPLES/MS), demonstrated for one substrate (AA) and its resultant products (eicosanoids). RAW cells were incubated in medium supplemented with deuterium-labeled AA. When the cells are stimulated, two sets of eicosanoids are produced, one from endogenous AA and the other from the supplemented (exogenous) deuterium-labeled form. This produces a signature mass spectral "doublet" pattern, allowing for a comprehensive and diverse eicosanoid search requiring no previous knowledge or assumptions as to what these species may be, in contrast to traditional methods. We report herein observing unexpected AA metabolites generated by the cells, some of which may constitute novel bioactive eicosanoids or eicosanoid inactivation metabolites, as well as demonstrating differing metabolic pathways for the generation of isomeric prostaglandins and potential peroxisome proliferator-activated receptor activators. Unexpectedly, we report observing a series of 1a, 1b-dihomologue prostaglandins, products of adrenic acid (22:4(n-6)), resulting from the two-carbon elongation of AA by the RAW cells.     

Eicosanoids mediate microaggregation reactions to bacterial challenge in isolated insect hemocyte preparations

Nodule formation is the quantitatively predominant insect cellular defense reaction to bacterial challenges, responsible for clearing the largest proportion of infecting bacteria from circulation. It has been suggested that eicosanoids mediate several steps in the nodulation process, including formation of hemocyte microaggregates, an early step in the process. While fat body and hemocytes are competent to biosynthesize eicosanoids, the source of the nodulation-mediating eicosanoids remains unclear. To investigate this issue, we studied hemocyte microaggregation reactions to bacterial challenge in vitro. Hemocyte suspensions from the tobacco hornworm, Manduca sexta, were treated with the phospholipase A(2) inhibitor, dexamethasone, then challenged with the bacterium Serratia marcescens. Preparations treated with dexamethasone yielded fewer hemocyte microaggregations than untreated, control preparations. Furthermore, the influence of dexamethasone was reversed by amending experimental (dexamethasone-treated) preparations with the eicosanoid biosynthesis precursor, arachidonic acid. Palmitic acid, which is not a substrate for eicosanoid biosynthesis, did not reverse the influence of dexamethasone on the microaggregation reaction. The influence of dexamethasone was also reversed by adding filtered media from challenged hemocyte preparations to dexamethasone-treated preparations. Finally, most hemocyte preparations treated with selected eicosanoid biosynthesis inhibitors formed fewer hemocyte microaggregations than control preparations. The 5- and 12-lipoxygenase inhibitor, esculetin, did not influence the formation of hemocyte microaggregations in this system. These results are consistent with similar investigations performed in vivo, and we infer that hemocytes are responsible for forming and secreting eicosanoids, which subsequently initiate nodulation by mediating hemocyte microaggregation.     

The Biological Significance of Prostaglandins and Related Eicosanoids in Invertebrates

SYNOPSIS. Prostaglandins and related eicosanoids are oxygenatedmetabolites of C20 polyunsaturated fatty acids. These compoundshave been detected in many vertebrate and invertebrate speciesthat represent all major phyla. The significance of eicosanoidsrelates to two broad areas of animal biology, one as mediatorsof crucial cellular events and another in mediation of certainecological interactions. Eicosanoids exert physiological actionsin reproduction, including release of egg-laying behavior insome insects, hatching in barnacles, egg-production in snails,spawning in bivalves, oocyte maturation in sea stars, and preventionof polyspermic fertilizations in sea urchin eggs. Eicosanoidsare also involved in salt and water transport physiology (insectsand bivalves), neurophysiology (mollusks) and cellular immunedefenses (insects). I propose that some eicosanoid actions arefundamental to animal physiology. Eicosanoids also mediate certainhost-parasite and predator-prey interactions. These includeskin penetration by blood fluke larvae, blood feeding by ticksand predator avoidance by certain octocoral and nudibranchs.Research in eicosanoids yields insights that help explain detailsof physiological and ecological phenomena in vertebrates andinvertebrates. Although we have seen considerable progress inour appreciation of eicosanoids in invertebrates, we are sorelylacking in our understanding of the biochemical mechanisms ofeicosanoid actions in invertebrates. I suggest that researchin this area will yield meaningful insights into the physiologyand ecology of invertebrates.