PubMed Health⌕ Search

Biomedical subjects

W R Henderson

Publications and source records attributed to W R Henderson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

Toxoplasma gondii tachyzoites markedly alter the profile of eicosanoids released by human mononuclear phagocytes. Freshly isolated, 2-h adherent human monocytes release both cyclooxygenase (e.g., thromboxane [TX] B2, prostaglandin [PG] E2) and 5-lipoxygenase (e.g., leukotriene [LT] B4, LTC4) products of arachidonic acid metabolism after stimulation by the calcium ionophore A23187 or ingestion of opsonized zymosan particles or heat-killed T. gondii. However, after incubation with viable T. gondii, normal and chronic granulomatous disease monocytes release only the cyclooxygenase products TXB2 and PGE2 and fail to form LTB4, LTC4, or other 5-lipoxygenase products. Monocytes maintained in culture for 5 d lose this capacity to release TXB2 and PGE2 after incubation with T. gondii. T. gondii significantly inhibit calcium ionophore A23187-induced LTB4 release by monocyte-derived macrophages; heat-killed organisms do not affect this calcium ionophore A23187-induced release of LTB4. T. gondii-induced inhibition of LTB4 release by calcium ionophore A23187-stimulated monocyte-derived macrophage is reversed by interferon (IFN)-gamma treatment of the monolayers. LTB4 induced extensive damage to the cellular membranes and cytoplasmic contents of the organisms as observed by transmission electron microscopy. Exogenous LTB4 (10(-6) M) induced intracellular killing of ingested T. gondii by non-IFN-gamma-treated monocyte-derived macrophages. IFN-gamma-induced antitoxoplasma activity in monocyte-derived macrophages was inhibited by the selective 5-lipoxygenase inhibitor zileuton but not by the cyclooxygenase inhibitor indomethacin. These findings suggest a novel role for 5-lipoxygenase arachidonic acid products in human macrophage IFN-gamma-induced antitoxoplasma activity.

Adult↗
PubMed1994

The role of leukotrienes in inflammation.

OBJECTIVE: To review the biochemistry and biological activities of leukotrienes, focusing on their role in the mediation of inflammatory diseases. DATA SOURCES: MEDLINE (1966-1994), EMBASE (Excerpta Medica; 1974-1994), and other biomedical and drug directory databases (such as Pharmaprojects and IMSworld R&D Focus [1991-1994]) were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on leukotrienes and related terms. STUDY SELECTION: Basic science studies on leukotrienes and clinical research studies on the use of leukotriene inhibitors and antagonists in the treatment of inflammatory diseases such as asthma, psoriasis, rheumatoid arthritis, and ulcerative colitis. DATA EXTRACTION: Detailed summaries of data from basic science studies on the formation and actions of leukotrienes and from clinical studies of drugs that block the synthesis or receptor-mediated actions of leukotrienes. DATA SYNTHESIS: Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid metabolism that are involved in the mediation of various inflammatory disorders. Of these, leukotriene B4 (a potent chemoattractant for leukocytes) and the sulfidopeptide leukotrienes C4, D4, and E4 (which increase vascular permeability and constrict smooth muscle) exert their biological actions through specific ligand-receptor interactions. Selective leukotriene inhibitors and receptor antagonists are currently under evaluation in the treatment of various inflammatory diseases. CONCLUSIONS: Further data on the in vitro and in vivo activities of the leukotriene inhibitors and antagonists should clarify the role of leukotrienes in the pathogenesis of such inflammatory diseases as asthma, rheumatoid arthritis, and inflammatory bowel disease. Leukotriene inhibitors and antagonists will probably become important agents in the group of anti-inflammatory drugs.

Animals↗
PubMed1994

Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects.

Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF.

Adolescent↗
PubMed1994

Inflammatory effects of ozone in the upper airways of subjects with asthma.

The objective of this study was to determine whether exposure to ozone causes inflammatory or functional changes in the upper or lower airways of asthmatic and nonasthmatic individuals. Ten asthmatic and eight nonasthmatic subjects were exposed to clean air, 120 ppb ozone, or 240 ppb ozone for 90 min during intermittent moderate exercise using a head dome exposure system. Pulmonary function tests, posterior rhinomanometry, and nasal lavage were performed before and after exposure. Leukocyte counts and chemotactic factors leukotriene B4 (LTB4), platelet-activating factor (PAF), and interleukin-8 (IL-8) were analyzed from nasal lavage fluid. In subjects with asthma, a significant increase (p < 0.05) in the number of white blood cells in lavage fluid was detected both immediately and 24 h after exposure to 240 ppb ozone, as was a significant increase in epithelial cells immediately after exposure (p < 0.05). No significant cellular changes were seen in nonasthmatic subjects. A significant correlation was observed between IL-8 and white blood cells counts after exposure to 240 ppb ozone (r = 0.76) in asthmatic subjects. No significant changes in pulmonary or nasal function or biochemical mediators were found in either the asthmatic or nonasthmatic subjects. These data indicate that asthmatic individuals are more sensitive to the acute inflammatory effects of ozone than nonasthmatic individuals.

Adolescent↗
PubMed1994

Role of leukotrienes in asthma.

The allergen-induced release of leukotrienes, the 5-lipoxygenase products of arachidonic acid metabolism in activated airway cells, is critical in the pathophysiology of asthma. Key proteins in leukotriene formation are 5-lipoxygenase and 5-lipoxygenase-activating protein. The leukotrienes have potent biologic activity: leukotriene (LT)B4 is a chemoattractant for leukocytes and also induces leukocyte aggregation and adherence to vascular endothelium; and the sulfidopeptide leukotrienes, LTC4, LTD4, and LTE4 are bronchoconstrictors, induce airway mucous secretion, and increase vascular permeability. Sulfidopeptide leukotriene release has also been shown to be important in the pathogenesis of asthmatic aspirin intolerance. Effective, selective inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein and leukotriene receptor antagonists have recently been developed as novel therapies for bronchial asthma and other inflammatory disorders.

Asthma↗
PubMed1993

Altered prostaglandin E2 regulation of cytokine production in atopic dermatitis.

The monocyte-derived inflammatory mediator, prostaglandin E2 (PGE2), can reduce IFN-gamma production, and this in turn may relate to IL-4 up-regulation of IgE synthesis and impaired delayed hypersensitivity in atopy. These abnormalities may relate to the cyclic nucleotide dysregulation in atopic dermatitis (AD), where monocyte cyclic AMP-phosphodiesterase (PDE) activity is increased and the consequent reduction in cAMP levels allows increased inflammatory responsiveness. In this study, we assessed the relationship between PGE2 and IFN-gamma production along with abnormal PDE activity in AD monocytes. Blood mononuclear leukocytes (MNL) from normal and AD donors were cultured for 24 hours, and supernatants were assayed for PGE2 and IFN-gamma by RIA. Spontaneous PGE2, but not leukotriene C4 release, was significantly increased in AD MNL (p < 0.05), although IFN-gamma levels were reduced (p < 0.05). In contrast, purified AD T cells, after removal of PGE2-producing monocytes, produced levels of IFN-gamma significantly higher than in normal T cell cultures. Inhibition of PGE2 synthesis by indomethacin caused increased IFN-gamma production by MNL cultures. We noted a strong negative correlation (r = 0.77) between PDE activity and IFN-gamma production in MNL cultures. We speculate that abnormal cyclic nucleotide metabolism caused by increased PDE activity may allow elevated levels of PGE2 production by AD monocytes. This study demonstrates a regulatory interaction between monocytes and T cells in AD and suggests that PGE2 may be an extracellular messenger between these cells to modulate IFN-gamma production.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in piglets.

Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF) alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗
PubMed1993

Lung mast cells increase in number and degranulate during pulmonary artery occlusion/reperfusion injury in dogs.

The role of mast cells in pulmonary artery occlusion/reperfusion injury was examined. Lung tissue was obtained from dogs after left pulmonary artery occlusion for 48 h (n = 5) or after similar occlusion followed by 4 h of reperfusion (n = 11). By light microscopy and morphometry, the percentage of mast cells increased 2.4-fold (p < 0.05) in nonoccluded right lungs and 2.9-fold (p < 0.05) in occluded left lungs without reperfusion compared with that in control lungs. After reperfusion, the occluded left lung contained 1.8-fold (p < 0.05) as many mast cells as the nonoccluded right lung and 4.2-fold (p < 0.05) more than that in control lungs. Hydroxyurea did not significantly affect the number of mast cells observed in the right and left lungs after ischemia/reperfusion; 39.8% and 54.4% of the mast cells were degranulated in nonoccluded right lung and occluded left lung preparations, respectively, after left pulmonary artery ischemia/reperfusion (each, p < 0.05 compared with control lungs). The release of eicosanoids into the airways during ischemia/reperfusion injury was also examined. Thromboxane B2 and leukotriene B4 were markedly increased (each, p < 0.05 compared with that in control lungs) in bronchial lavage fluids from both nonoccluded and occluded lungs compared with sham-occluded lungs. Thus, mast cell recruitment and degranulation may play a role in lung ischemia/reperfusion injury.

Animals↗
PubMed1992

Toxoplasma gondii stimulates the release of 13- and 9-hydroxyoctadecadienoic acids by human platelets.

We have recently demonstrated a novel cytotoxic effect of human platelets against Toxoplasma gondii and a role for thromboxane (TX) in this process (Yong et al., 1991). We now report on the spectrum of lipid mediators released by human platelets after interaction with T. gondii. In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography. Thermospray-liquid chromatography/mass spectrometry analysis and straight-phase HPLC identified the unknown peak as a mixture of 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE. Radiolabeling studies with [14C]linoleic acid indicated that the platelets were the cellular source of the octadecanoids with 13-HODE (87.7%) greater than 9-HODE (12.3%). Inhibitor studies with indomethacin indicated that 13-HODE was a lipoxygenase product and 9-HODE was a cyclooxygenase product of linoleic acid. Thus, Toxoplasma-stimulated platelets release oxygenated products of both arachidonic acid and linoleic acid which may be important in the host response to T. gondii infection.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Human spermatozoa produce C16-platelet-activating factor.

Recent data indicate that human spermatozoa produce platelet-activating factor as determined by the rabbit platelet [3H]serotonin release bioassay. In this report, we examined by fast atom bombardment/mass spectrometry the molecular species of platelet-activating factor generated by these germ cells. Extracted spermatozoal samples that contained platelet-activating factor bioactivity underwent straight-phase high-performance liquid chromatography, and fractions which coeluted with authentic C16- and C18-platelet-activating factor standards were subjected to fast atom bombardment/mass spectrometry. Our mass spectral data indicate that human spermatozoa synthesize C16-platelet-activating factor but not C18-platelet-activating factor.

Fatty Acids↗
PubMed1992

Degranulation of cystic fibrosis nasal polyp mast cells.

The ultrastructure of nasal polyps from cystic fibrosis (CF) patients was compared with non-CF nasal polyps in this study. Morphometric analysis showed that CF nasal polyps contained greater numbers of mast cells, endothelial cells, lymphocytes, and plasma cells compared with the non-CF specimens. Morphologic evidence of degranulation was seen in approximately 30 per cent of the CF mast cells but was not observed in the non-CF mast cells. Increased numbers of small granules, vacuolated granules, and lipid bodies were noted in the CF compared with the non-CF nasal polyp mast cells. Also observed was a decrease in collagen in the extracellular space of the CF nasal polyps compared with the non-CF specimens. Although eosinophils were observed in the non-CF nasal polyp tissue, these leukocytes were absent in the CF nasal polyps. These data indicate that striking morphologic differences exist between CF and non-CF nasal polyps with mast cell degranulation, a salient feature of CF specimens.

Adolescent↗
PubMed1992

Acute changes in vasoactive lipid mediators in experimental hyaline membrane disease.

Endothelial release of the arachidonate derivative PGI2 may be increased in response to cyclic lung stretching. We therefore sought to determine if the stable metabolite of PGI2, 6-keto-PGF1 alpha, would be found in increased quantities in primates ventilated with conventional mechanical ventilation (CMV) compared to treatment with high frequency oscillatory ventilation (HFOV). We also sought to determine if other membrane-derived vasoactive substances such as LTC4, PAF and TXB2 would be elevated in plasma and lung tissue of animals developing hyaline membrane disease (HMD) and if the levels would correlate with the severity of the respiratory distress. Twenty prematurely delivered monkeys were treated with either CMV or HFOV from the first breath after Cesarean delivery until sacrifice at 6 h of age. We found a significant increase from birth to 5 min and from 5 min to 5 h in 6-keto-PGF1 alpha, and a significant increase from 5 min to 5 h in TXB2. We found a significant decline from cord blood to 5 min of LTC4, without further change by 5 h. PAF was present in all plasma samples but showed no upward or downward trend. There was no difference in the 5-h plasma level or in the lung homogenate level of any of the lipid mediators between the two types of assisted ventilation. There was no correlation between any lipid mediator level and severity of the HMD, as measured by gas exchange, radiographic or histologic criteria, when assessed by each ventilator group alone or with both groups combined. We conclude that the immediate postnatal increases in TXB2 and PGI2 and decrease in LTC4 are not altered substantially by use of HFOV.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Cytotoxic activity of 13-hydroxyoctadecadienoic acid against Toxoplasma gondii.

Recent data indicate that platelets may play an important role in the host defence against Toxoplasma gondii infections. T. gondii-stimulated human platelets release thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-HETE) from arachidonic acid and 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid (Yong et al. 1991; Henderson et al. 1992). We have previously demonstrated that the eicosanoid TXA2 has potent cytotoxic activity against T. gondii trophozoites (Yong et al. 1991). In this study, we examined whether 12-HETE, 13-HODE, and linoleic acid also have toxoplasmacidal activity. 13-HODE at concentrations > or = 10(-8) M rapidly induced cytotoxic changes in T. gondii. Ultrastructural changes induced by 13-HODE in T. gondii included an initial leakage of cytoplasmic contents into a space between the inner and outer parasite bilayer membrane units which was followed by intracellular vacuolation and loss of cytoplasmic contents. In contrast, linoleic acid and 12-HETE lacked toxoplasmacidal activity at 10(-10)-10(-6) M concentrations. These data indicate that 13-HODE, a product of linoleic acid metabolism, has potent cytotoxic activity against T. gondii; this toxoplasmacidal activity may be important in the inflammatory response to this pathogen.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Effect of pentoxifylline on cytokine- and eicosanoid-induced acute pulmonary hypertension in piglets.

The methylxanthine derivative pentoxifylline (PTF) demonstrates vasodilatory properties in vivo. We tested the hypothesis that PTF infusion would blunt or inhibit tumor necrosis factor-alpha (TNF alpha)-induced and U46,619-induced increases in mean pulmonary artery pressure and pulmonary vascular resistance (PVR) in the neonatal piglet and would do so by altering production of eicosanoid vasoactive mediators. Anesthetized, paralyzed piglets (age 10-29 d) were randomized and treated with a 30-min infusion of TNF alpha alone (n = 13 animals), with a combination of TNF alpha plus pretreatment and continuous infusion with PTF (n = 6), or with a combination of U46,619 for 30 min plus pretreatment and continuous infusion of PTF (n = 5). There was no difference in pulmonary or systemic hemodynamic indices between the three groups at baseline. PVR was significantly elevated at 15 min and at 2 h in the TNF alpha-only group. The TNF alpha-induced rise in mean pulmonary artery pressure and PVR was inhibited by the PTF until 2 h, by which time PVR was elevated above baseline and was comparable to the value found in animals treated with only TNF alpha. PTF produced no inhibition in the U46,619-induced elevation of PVR during the 30-min simultaneous treatment. In the PTF + TNF alpha group, mean systemic blood pressure declined to 50% of baseline value (p less than 0.02) by 2 h of age. No significant decline was noted in mean systemic arterial pressure of the TNF alpha-only or the U46,619-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Group B streptococcal sepsis in piglets: effect of combined pentoxifylline and indomethacin pretreatment.

Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiology in human newborns and neonatal animal models of sepsis. Animal models of GBS sepsis demonstrate a two-phase response: 1) an acute phase (less than 1 h) of increased pulmonary artery pressure (Ppa) and reduced arterial oxygen pressure (PaO2) that is associated with increased serum thromboxane B2 (TxB2) and 2) a late phase (2-4 h) of persistently increased Ppa and reduced PaO2, reduced systemic arterial pressure, and progressive fall in cardiac output that is associated with increased serum TxB2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and tumor necrosis factor-alpha (TNF alpha). We hypothesized that pretreatment of piglets with both pentoxifylline (PTF), an inhibitor of TNF alpha production and activity, and indomethacin (INDO) would 1) inhibit GBS-induced TxB2, 6-keto-PGF1 alpha, and TNF alpha and 2) prevent both the acute- and late-phase physiologic responses of GBS sepsis. Combined PTF and INDO pretreatment of anesthetized, mechanically ventilated piglets infused with GBS (1.25 x 10(9) colony forming units/kg/h) for 4 h prevented GBS-induced increases in Ppa at 1 h (GBS + PTF + INDO: 1.8 +/- 0.07 kPa versus GBS alone: 4.7 +/- 0.1 kPa) and markedly attenuated increases in Ppa at 4 h (GBS + PTF + INDO: 2.1 +/- 0.1 kPa versus GBS alone: 4.4 +/- 0.1 kPa).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Swyer-James syndrome: CT findings in eight patients.

To determine the importance of chest CT findings in patients with Swyer-James syndrome (unilateral small lung with air trapping) and to compare these findings with those on chest radiographs and scintigrams, we reviewed the CT scans, chest radiographs, and scintigrams of eight patients with the syndrome. Radiographs showed unilateral hyperlucency in seven patients and bilateral asymmetric hyperlucency in one. CT showed that the hyperlucency was unilateral in only three and that hyperlucency in one. CT showed that the hyperlucency was unilateral in only three and that hyperlucent regions on radiographs contained patches of normal lung attenuation in five patients. Conversely, in four patients, CT also showed small hyperlucencies in regions considered normal on radiographs. These lucencies usually had poorly defined margins and irregular shapes (five patients), but sometimes were peripheral, wedge shaped, and sharply demarcated (two patients). CT also showed subtle abnormalities not visible on radionuclide scans in two patients. Air trapping in hyperlucent regions was confirmed by a lack of change in volume on expiratory CT scans in five cases. Bronchiectasis was found in only three patients. CT helps to exclude central bronchial obstruction, cysts, and vascular disease as causes of hyperlucency. By excluding central obstruction, CT may make bronchoscopy unnecessary in some patients. CT is more sensitive than radiographs and radionuclide scans in detecting hyperlucent regions and in showing their distribution. Our experience suggests that bronchiectasis is not a necessary component of the Swyer-James syndrome.

Adolescent↗
PubMed1991

Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane.

Human platelets, in the absence of antibody, are cytotoxic to tachyzoites of Toxoplasma gondii as determined by vital staining, transmission electron microscopy, and the failure of Toxoplasma to survive and replicate in mice after in vitro interaction of the organisms with platelets. Platelet to T. gondii ratios as low as 1:3 were toxic to the organisms with direct cell-cell contact essential for platelet-mediated cytotoxicity. Adherence of platelets to T. gondii and disruption of surface membranes and cytoplasmic contents of the organisms were observed ultrastructurally. Reactive oxygen species were not implicated in the platelet-mediated toxicity. The interaction of T. gondii with platelets resulted in a marked increase in thromboxane B2 (TXB2) production compared with that by unstimulated platelets. The cyclooxygenase inhibitors acetylsalicylic acid and indomethacin inhibited platelet-mediated cytolytic activity as did the selective TXA2 synthetase inhibitor dazmegrel, indicating a role for thromboxane in the platelet-induced cytotoxicity. Further, toxoplasmacidal activity was retained in the TXA2 synthetase-containing microsomal fractions of platelets disrupted by freezing and thawing; cytolytic activity was absent in microsome-depleted platelet supernatant fractions. Both the TXA2-generating platelet microsome system and a stable TXA2 analogue induced damage to the cellular membranes of the Toxoplasma as noted by transmission electron microscopy. These findings suggest that platelets may play a role in the host defense against Toxoplasma and that release of thromboxane may be important in this cytolytic process.

Animals↗