leukotriene-b4 and Wounds-and-Injuries

The leukotrienes (LTs) are 5-lipoxygenase metabolites of arachidonic acid. The synthesis and release of LTs have been demonstrated in many cells and organs, and LTs are considered to be normal products of continuous metabolism of arachidonic acid. However, although evidence in favor of a critical role for LTs in regulation of physiological functions is still scarce, a growing body of evidence suggests a role for LTs in mediation of several pathophysiological processes such as generalized or local immune reactions, inflammation, asthma, shock, and trauma. LTs have been shown to have potent actions on many essential organs and systems, including the cardiovascular system (heart, blood vessels, microcirculation), the pulmonary system (lung, airways), the central nervous system (neural, glial, and vascular elements), the gastrointestinal tract, and the immune system. In these organs the effects of LTs are mediated by specific LT receptors. Identification of LTs and characterization of their regional and systemic pathological effects, together with characterization of their receptors and elucidation of their structure-activity relationships, are fundamental to developing LT antagonists or synthesis inhibitors that might prevent or reverse LT-dependent reactions. Preliminary reports have already shown that such pharmacological agents ameliorate some aspects of disease processes in experimental animals as well as in humans. In this brief review we intend to highlight the evidence that implicates LTs in normal physiological functions as well as in disease processes.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Central Nervous System; Central Nervous System Diseases; Humans; Hypersensitivity; Inflammation; Leukotriene B4; Respiration Disorders; Respiratory Physiological Phenomena; SRS-A; Vasomotor System; Wounds and Injuries

Topics: Animals; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Binding Sites; Cytochrome P-450 Enzyme System; Fatty Acids, Essential; Humans; Kinetics; Leukotriene B4; Lipoxygenase; Prostaglandin-Endoperoxide Synthases; SRS-A; Wounds and Injuries

Post-operative pain and inflammation are frequently managed with non-steroidal anti-inflammatory drugs (NSAIDs). Despite the prevalence of their use, however, relatively little is known about in vivo tissue concentrations of inflammatory mediators at the site of tissue injury and their modulation by NSAIDs. This study compares the effect of oral administration of the NSAID flurbiprofen, to placebo, on tissue levels of immunoreactive prostaglandin E2 (iPGE2), leukotriene B4 (iLTB4), and (S)-flurbiprofen within the surgical wound using implanted microdialysis probes in the dental impaction pain model. Twenty-four healthy patients in need of extraction of partial to complete bony mandibular third molars were recruited for this randomized, double-blind, placebo-controlled study. Following pre-operative administration of N2O/O2, midazolam i.v., and regional block anesthesia with 3% mepivacaine, each patient underwent surgical removal of their impacted third molars. Immediately following completion of the surgery, two semi-permeable microdialysis probes (3 kDa molecular weight cut-off) were implanted into each mandibular surgical site. Patients were taken to a recovery room and microdialysis samples and patient pain reports (visual analog scale, VAS) were collected at 30 min intervals for 4 h. Patients randomly received either flurbiprofen (200 mg orally) or placebo at the onset of post-operative pain. Dialysate samples were collected, frozen, and later assayed for iPGE2, iLTB4, and (S)-flurbiprofen levels. Results of this study show that flurbiprofen decreased post-operative pain by approximately 70% compared to placebo-treated patients (P < 0.001). During the 4 h post-operative timecourse of this study, flurbiprofen treatment significantly reduced peak tissue levels of iPGE2 (9.2 +/- 2.6 vs. 0.4 +/- 0.15 nM; P < 0.001), without having a significant effect on peak tissue levels of iLTB4 (2.5 +/- 1.4 vs. 1.49 +/- 0.86 nM) compared to placebo treatment. Levels of (S)-flurbiprofen significantly increased within the surgical wound exceeding therapeutic levels by 60 min after administration. Flurbiprofen is able to significantly suppress the local production of iPGE2 and provide significant analgesic efficacy without altering iLTB4 tissue levels in this model of acute post-operative inflammatory pain. These data indicate that NSAIDs selectively alter eicosanoid levels within surgical wound and evoke analgesia at time points coincident with elevated wound levels of

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Dinoprostone; Double-Blind Method; Flurbiprofen; Humans; Immunohistochemistry; Leukotriene B4; Microdialysis; Molar, Third; Tooth Extraction; Tooth, Impacted; Wounds and Injuries

Neutrophils are major inflammatory cells that rapidly infiltrate wounds to provide antimicrobial functions. Within the damaged tissue, neutrophil migration behavior often switches from exploratory patrolling to coordinated swarming, giving rise to dense clusters that further disrupt tissue architecture. This aggregation response is self-organized by neutrophil paracrine chemoattractant signaling (most notably of the inflammatory mediator leukotriene B4 [LTB4]). The coordination mechanism and possible evolutionary benefits of neutrophil swarms are elusive. Here, we show that neutrophil swarms require mutual reinforcement of damage signaling at the wound core. New biosensors and live imaging in zebrafish revealed that neutrophil chemoattractant synthesis is triggered by a sustained calcium flux upon contact with necrotic tissue that requires sensing of the damage signal ATP. This "calcium alarm" signal rapidly propagates in the nascent neutrophil cluster in a contact-dependent manner via connexin-43 (Cx43) hemichannels, which are mediators of active ATP release. This enhances chemoattractant biosynthesis in the growing cluster, which is instrumental for coordinated motion and swarming. Inhibition of neutrophil Cx43 compromises clearance of wound-colonizing P. aeruginosa bacteria and exacerbates infection-induced morbidity. Thus, cooperative production of alarm signals among pioneer clustering neutrophils fuels the growth of dense antimicrobial cell masses that effectively seal off breached tissue barriers from opportunistic pathogens.

Topics: Adenosine Triphosphate; Animals; Calcium; Cell Aggregation; Connexin 43; Connexins; Leukotriene B4; Neutrophil Infiltration; Neutrophils; Pseudomonas aeruginosa; Signal Transduction; Wounds and Injuries; Zebrafish

Trauma causes inflammation by releasing mitochondria that act as Danger-Associated Molecular Patterns (DAMPs). Trauma also increases susceptibility to infection. Human mitochondria contain 13 N-formyl peptides (mtFPs). We studied whether mtFPs released into plasma by clinical injury induce neutrophil (PMN) inflammatory responses, whether their potency reflects their similarity to bacterial FPs and how their presence at clinically relevant concentration affects PMN function.. N-terminal sequences of the 13 mtFPs were synthesized. Changes in human PMN cytosolic Ca concentration ([Ca]i) and chemotactic responses to mtFPs were studied. Sequence similarity of mtFPs to the canonical bacterial peptide f-Met-Leu-Phe (fMLF/fMLP) was studied using the BLOcks SUbstitution Matrix 62 (BLOSUM 62) system. The presence of mtFPs in plasma of trauma patients was assayed by Enzyme-linked immunosorbent assay (ELISA). The effects of the most potent mtFP (ND6) on PMN signaling and function were then studied at ambient clinical concentrations by serial exposure of native PMN to ND6, chemokines and leukotrienes.. Five mtFPs (ND6, ND3, ND4, ND5, and Cox 1) induced [Ca]i flux and chemotaxis in descending order of potency. Evolutionary similarity to fMLF predicted [Ca]i flux and chemotactic potency linearly (R = 0.97, R = 0.95). Chemoattractant potency was also linearly related to [Ca]i flux induction (R = 0.92). Active mtFPs appear to circulate in significant amounts immediately after trauma and persist through the first week. The most active mtFP, ND6, suppresses responses to physiologic alveolar chemoattractants (CXCL-1, leukotriene B4) as well as to fMLF where CXCL-1 and leukotriene B4 do not suppress N-formyl peptide receptor (FPR)-1 responses to mtFPs. Prior FPR-1 inhibition rescues PMN from heterologous suppression of CXCR-1 and BLT-1 by mtFPs.. The data suggest mtFPs released by injured tissue may attract PMN to trauma sites while suppressing PMN responses to other chemoattractants. Inhibition of mtFP-FPR1 interactions might increase PMN recruitment to lung bacterial inoculation after trauma. These findings suggest new paradigms for preventing infections after trauma.. Therapeutic, Level IV.

Topics: Calcium; Cells, Cultured; Chemokine CXCL1; Chemotaxis; Computational Biology; Cyclooxygenase 1; Cytosol; Electron Transport Complex I; Evolution, Molecular; Humans; Leukotriene B4; Mitochondria; Mitochondrial Proteins; N-Formylmethionine Leucyl-Phenylalanine; NADH Dehydrogenase; Neutrophils; Peptides; Receptors, Formyl Peptide; Signal Transduction; Wounds and Injuries

Recognizing patients at risk for pulmonary complications (PC) is of high clinical relevance. Migration of polymorphonuclear leukocytes (PMN) to inflammatory sites plays an important role in PC, and is tightly regulated by specific chemokines including interleukin (IL)-8 and other mediators such as leukotriene (LT)B4. Previously, we have reported that LTB4 indicated early patients at risk for PC after trauma. Here, the relevance of LTB4 to indicating lung integrity in a newly established long-term porcine severe trauma model (polytrauma, PT) was explored.. Twelve pigs (3 months old, 30 ± 5kg) underwent PT including standardized femur fracture, lung contusion, liver laceration, hemorrhagic shock, subsequent resuscitation and surgical fracture fixation. Six animals served as controls (sham). After 72h lung damage and inflammatory changes were assessed. LTB4 was determined in plasma before the experiment, immediately after trauma, and after 2, 4, 24 or 72h. Bronchoalveolar lavage (BAL)-fluid was collected prior and after the experiment.. Lung injury, local gene expression of IL-8, IL-1β, IL-10, IL-18 and PMN-infiltration into lungs increased significantly in PT compared with sham. Systemic LTB4 increased markedly in both groups 4h after trauma. Compared with declined plasma LTB4 levels in sham, LTB4 increased further in PT after 72h. Similar increase was observed in BAL-fluid after PT.. In a severe trauma model, sustained changes in terms of lung injury and inflammation are determined at day 3 post-trauma. Specifically, increased LTB4 in this porcine long-term model indicated a rapid inflammatory alteration both locally and systemically. The results support the concept of LTB4 as a biomarker for PC after severe trauma and lung contusion.

Topics: Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Humans; Inflammation; Interleukins; Leukotriene B4; Lung; Lung Injury; Neutrophils; Swine; Wounds and Injuries

Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic.

Topics: Animals; Benzoates; Cell Adhesion Molecules; Cells, Cultured; Endothelial Cells; Humans; Immunoglobulins; Intercellular Junctions; Leukocyte Elastase; Leukotriene B4; Macrophage-1 Antigen; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Reperfusion Injury; Transendothelial and Transepithelial Migration; Venules; Wounds and Injuries

Leukotriene B4 (LTB4), a proinflammatory lipid mediator correlates well with the acute phase of Acute Respiratory Distress Syndrome (ARDS). Therefore, LTB4-levels were investigated to determine whether they might be a useful clinical marker in predicting pulmonary complications (PC) in multiply traumatized patients.. Plasma levels of LTB4 were determined in 100 patients on admission (ED) and for five consecutive days (daily). Twenty healthy volunteers served as control. LTB4-levels were measured by ELISA. Thirty patients developed PC (pneumonia, respiratory failure, acute lung injury (ALI), ARDS, pulmonary embolism) and 70 had no PC (ØPC).. LTB4-levels in the PC-group [127.8 pg/mL, IQR: 104-200pg/ml] were significantly higher compared to the ØPC-group on admission [95.6 pg/mL, IQR: 55-143 pg/mL] or control-group [58.4 pg/mL, IQR: 36-108 pg/mL]. LTB4 continuously declined to basal levels from day 1 to 5 without differences between the groups. The cutoff to predict PC was calculated at 109.6 pg/mL (72% specificity, 67% sensitivity). LTB4 was not influenced by overall or chest injury severity, age, gender or massive transfusion. Patients with PC received mechanical ventilation for a significantly longer period of time, and had prolonged intensive care unit and overall hospital stay.. High LTB4-levels indicate risk for PC development in multiply traumatized patients.

Topics: Acute Lung Injury; Adult; Blood Transfusion; Critical Care; Enzyme-Linked Immunosorbent Assay; Female; Hospitalization; Humans; Leukotriene B4; Lung Diseases; Male; Middle Aged; Respiratory Distress Syndrome; Sensitivity and Specificity; Time Factors; Wounds and Injuries

G protein-coupled chemoattractants recruit neutrophils (PMN) to sites of injury and infection. The leukotrienes (LT) and CXC chemokines (CXC) and their receptors (BLT1/BLT2 and CXCR1/CXCR2) are all known to play roles in these responses. Each system has been studied separately in vitro, but in vivo they act concurrently, and the clinical interactions between the two systems are unstudied. We prospectively studied calcium mobilization and chemotactic responses to LTB(4) in PMN from major trauma patients. The responses of the high affinity BLT1 receptor were suppressed at the 3-day postinjury time point, but recovered by 1 wk. Trauma patients had transient elevations of plasma LT and CXC levels. Functional deficits identical with those in trauma PMN were reproduced in vitro by exposing healthy PMN to CXCs at the elevated plasma concentrations found. Functional responses to LTB(4) were suppressed by cross-talk with CXC and BLT2 receptors that desensitize BLT1. Since the suppression of intracellular calcium mobilization was prominent, we also studied the role of suppressed cell calcium mobilization in the defective chemotactic responses to LTB(4). We noted that PMN chemotaxis to LTB(4) showed far more dependence on store-operated calcium entry than on the release of cellular calcium stores, and that store-operated calcium responses to BLT1 activation were markedly inhibited during the same time period as was chemotaxis. The intermittent release of inflammatory mediators after injury can blunt PMN responses to LTs by suppressing BLT1 as well as downstream calcium entry. Diminished LT receptor activity due to cross-talk with CXC receptors can inhibit PMN recruitment to infective sites. This may predispose injured patients to septic complications.

Topics: Adolescent; Adult; Aged; Calcium; Calcium Signaling; Chemotaxis, Leukocyte; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Male; Middle Aged; Neutrophils; Prospective Studies; Receptor Cross-Talk; Receptors, Chemokine; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Receptors, Leukotriene B4; Wounds and Injuries

Prostaglandin E(2) (PGE(2)) production after trauma contributes to immune alterations that increase susceptibility to infections. We hypothesize that blocking PGE(2) with NS-398, a selective COX-2 inhibitor, will modulate this response and improve outcome. This study evaluated the effect of NS-398 given over 7 days on proinflammatory cytokines, intracellular signaling, and survival after a septic challenge. Balb/C mice (n = 8/group) were given 10 mg/kg NS-398 intraperitoneally over 7 days, starting after anesthesia or trauma (femur fracture + 40% hemorrhage). Four groups, anesthesia + vehicle (C), anesthesia + NS-398 (CN), trauma + vehicle (T), or trauma + NS-398 (TN), were studied. On Day 7 after trauma, mice were sacrificed, serum was collected, and splenic macrophages were evaluated for PGE(2), LTB(4), IL-6, TNF-alpha, and NO production. Additionally, macrophage COX-2 mRNA, IkappaB-alpha, and NF-kappaB were evaluated. In a separate study, mice (n = 10-11/group) were traumatized and given NS-398 over 7 days, and then cecal ligation and puncture (CLP) were performed. Mice were then followed for survival over 10 days (via log-rank test). NS-398 treatment of injured mice decreased PGE(2) production compared to T (3.9 +/- 0.3 vs 3.1 +/- 0.4 pg/microg protein), and significantly decreased IL-6, NO, and TNF-alpha production. NS-398 treatment also attenuated COX-2 mRNA levels and NF-kappaB activation. These cellular events correlate with a significant survival advantage in TN versus T mice after CLP. These data suggest that a specific COX-2 inhibitor not only suppresses PGE(2), but normalizes proinflammatory cytokines after trauma through changes that may partly be mediated via transcriptional events. This correlates with significantly increased survival in TN mice given a septic challenge and suggests that COX-2 inhibitors contribute to modulating the inflammatory response and improving survival after trauma.

Topics: Animals; Bacterial Infections; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Female; Femoral Fractures; Interleukin-6; Isoenzymes; Leukotriene B4; Macrophages; Mice; Mice, Inbred BALB C; NF-kappa B; Nitric Oxide; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Spleen; Sulfonamides; Survival Analysis; Tumor Necrosis Factor-alpha; Wounds and Injuries

Chemotaxins from inflammatory sites prime or activate neutrophils (PMN) by using cytosolic calcium ([Ca2+]i) fluxes as second messengers. [Ca2+]i can be mobilized rapidly by receptor-mediated entry or store-release, or more slowly by store-operated calcium influx (SOCI). We studied [Ca2+]i mobilization by chemotaxins and how trauma impacts the calcium entry mechanisms used by chemotaxins.. [Ca2+]i flux was studied by spectrofluorometry. The contributions of early and late [Ca2+]i currents to net calcium flux were compared after stimulation by more potent (fMLP, C5a, PAF) or less potent (IL-8, GRO-alpha, and LTB4) agonists. Store operated [Ca2+]i mobilization was reflected by the ratio of area under the [Ca2+]i efflux curve to peak [Ca2+]i (efflux curve). PMN from trauma patients (ISS > 25) and pair-matched volunteer (n = 7 pairs) were then primed and stimulated with thapsigargin to compare cell calcium stores and SOCI.. Late [Ca2+]i mobilization made more important contributions to fMLP, PAF, and C5a signals than to IL-8, GRO-alpha, or LTB4 (p < 0.01 all comparisons). Calcium stores and store release were only marginally lower after injury (p = not significant), but trauma PMN showed far higher [Ca2+]i influx after thapsigargin (p = 0.007), and greater net SOCI (p = 0.034).. SOCI may play an important role in PMN activation, and trauma increases PMN SOCI. Prolonged elevations of [Ca2+]i due to enhanced SOCI may alter stimulus-response coupling to chemotaxins and contribute to PMN dysfunction after injury.

Topics: Adult; Calcium; Complement C5a; Female; Humans; In Vitro Techniques; Interleukin-8; Leukotriene B4; Male; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activating Factor; Spectrophotometry; Wounds and Injuries

The pathogenesis of multiple organ failure after injury is believed to involve priming and activation of the inflammatory cascade, and the polymorphonuclear neutrophil (PMN) appears to be an integral effector. Characterization of the primed PMN is evolving. Because much research has focused on the respiratory burst, the synergistic role of cytotoxic proteases, especially elastase, has been largely ignored. In addition, CD11b has been identified as pivotal in PMN-mediated tissue injury. Our hypothesis is that the well-recognized postinjury mediators platelet-activating factor (PAF) and leukotriene B4 (LTB4) prime PMNs for the concordant release of elastase and superoxide (O2-) as well as for CD11b up-regulation.. Human PMNs were isolated and then incubated with PAF or LTB4 before N-formyl-methionyl-leucyl-phenylalanine activation. O2- generation was measured by reduction of cytochrome c. Elastase was measured by cleavage of Ala-Ala-Pro-Val p-nitroanilide. CD11b expression was quantified by incubation with R-phycoerythrin-labeled monoclonal antibodies followed by flow cytometry.. PAF and LTB4 primed PMNs maximally within 5 minutes for the production of O2-, elastase release, and simultaneous up-regulation of CD11b expression on the PMN surface.. PAF and LTB4 prime human PMNs for the concordant release of elastase, generation of O2-, and CD11b up-regulation. Understanding the physiologic characteristics of PMN priming may offer new therapeutic targets to avoid the development of multiple organ failure after injury.

Topics: Humans; Inflammation; Leukocyte Elastase; Leukotriene B4; Macrophage-1 Antigen; Multiple Organ Failure; Neutrophils; Platelet Activating Factor; Respiratory Burst; Superoxides; Wounds and Injuries

Leukotriene B4 (LTB4) in skin samples from seven forensic cases was detected by HPLC to distinguish their antemortem or postmortem origin. In total, there were thirteen antemortem and seven postmortem specimens. The results showed that LTB4 was found in all antemortem wound specimens which were either fresh, or refrigerated or fixed in formalin for less than 10 days. In contrast, LTB4 could not be detected in postmortem wound specimens. These results suggested that detecting the content of LTB4 is a useful method for distinguishing antemortem from postmortem injuries.

Topics: Adult; Aged; Child; Chromatography, High Pressure Liquid; Female; Humans; Leukotriene B4; Leukotriene C4; Male; Postmortem Changes; Prostaglandins B; Skin; Time Factors; Wounds and Injuries

Topics: Burns; Cardiopulmonary Bypass; Humans; Leukotriene B4; Leukotriene C4; Neutrophils; Wounds and Injuries

Thirty multiply injured blunt-trauma patients at high risk for development of ARDS (multisystem trauma including more than one organ or extremity, Injury Severity Score of 26 or more, hypotension and need for 1500 mL or more blood within the first hour after admission, and PaO2 less than or equal to 70 torr) were studied sequentially with blood and physiologic evaluations beginning immediately after injury and every eight hours for eight days, or until death, to study the evolution of the ARDS process. Mixed venous blood samples were obtained for eicosanoids PGE2, PGF2 alpha, thromboxane B2, PGI2 (6-KetoPGF1 alpha) and leukotriene B4 (LTB4). Platelet (PLAT), and neutrophil (WBC) counts were also done and plasma elastase was measured. At 7:00 AM each day patient neutrophils were obtained for a study of zymosan-activated superoxide production using a chemiluminescence assay. These data were correlated with physiologic measurements of the Respiratory Index (RI), per cent pulmonary shunt (QS/QT), and respiratory compliance measures. Seven patients developed a fulminant post-traumatic ARDS syndrome within 96 hours after injury. Twelve patients without ARDS developed sepsis (TS) four or more days after injury, and 11 had uncomplicated postinjury courses (TR). Compared to both TR and TS, ARDS had a significant (p less than 0.01) rise in neutrophil superoxide production beginning on day 2 through day 4 after injury. This was preceded by rises in PGE2 and LTB4, which were significantly correlated with subsequent falls in PLAT and WBC and rises in TXB2, PGF1, and superoxide production and followed by increases in RI, QS/QT, and a fall in compliance. The significant difference in the pattern and sequence of events in ARDS compared to TR and TS patients suggests that in ARDS the earliest event may be related to peripheral release of PGE2 and LTB4 due to platelet activation and lung sequestration with release of PGF2 alpha, and by aggregation and leukocyte adherence with release of elastase. However, fulminant ARDS mortality appears to be related to the subsequent amplification of the LTB4 leukocyte activation with superoxide production that does not achieve significance before the second day after injury and rises to a maximum by day 4 after injury. These data suggest that post-trauma ARDS follows a different evolutionary pattern than that reported in animal models and is also different from that seen in human TS or TR patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Biomechanical Phenomena; Blood Platelets; Cell Communication; Humans; Infections; Leukotriene B4; Neutrophils; Prostaglandins; Respiratory Distress Syndrome; Statistics as Topic; Superoxides; Thromboxane B2; Time Factors; Wounds and Injuries

The generation and metabolism of leukotrienes (LTs) from polymorphonuclear granulocytes of four polytraumatic patients on stimulation with the Ca-Ionophore A 23187 were studied by high performance liquid chromatography. In contrast to healthy donors the concentration of LTB4 within the supernatant of the stimulated granulocytes from these patients is reduced. The ratio of LTB4 versus the combined amounts of the biologically inactive 6-trans and 12-epi-6-trans-isomers is significantly decreased. In one patient who suffered from an Adult Respiratory Distress Syndrome (ARDS) a pronounced enhancement of LTC4 synthesis was observed.

Topics: Calcimycin; Chromatography, High Pressure Liquid; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Neutrophils; SRS-A; Stereoisomerism; Wounds and Injuries

The study concerned the effect of arachidonic acid metabolites on the inflammatory reaction in granulation tissue of open wounds in rats. Metabolites or inhibitors were applied in a wound chamber attached to circular, open, full-thickness skin wounds 5 days post-wounding. The adjacent wound served as control. Blood flow, albumin extravasation and accumulation of polymorphonuclear leucocytes (PMNLs) were measured in the granulation tissue. Prostaglandin E2 (PGE2 5.7 microM) increased blood flow and albumin extravasation by 95 and 16%, respectively, without affecting PMNLs. Leukotriene B4 (LTB4 2.7 microM) increased PMNL accumulation by 142% without altering albumin extravasation. Indomethacin (28 microM, repeatedly) did not affect blood flow or albumin extravasation, but increased PMNL accumulation by 21%. Methylprednisolone (3.3 mM, repeatedly) reduced blood flow and albumin extravasation by 29 and 31%, respectively, without influencing PMNLs. The granulation tissue obviously responds to exogenous PGE2 and LTB4. Endogenous arachidonic acid metabolites seem to play only a minor role in the inflammatory process in this model.

Topics: Animals; Arachidonic Acids; Biotransformation; Dinoprostone; Granulation Tissue; Indomethacin; Inflammation; Leukotriene B4; Male; Methylprednisolone; Neutrophils; Prostaglandins E; Rats; Rats, Inbred Strains; Regional Blood Flow; Wound Healing; Wounds and Injuries