Lipid mediators , tumor necrosis factor and nitric oxide and their interactions in immune complex induced lung injury. (1998 Dec)
lipid mediators , tumor necrosis factor and nitric oxide and their interactions in immune complex induced lung injury . We investigated the contribution of eicosanoids , platelet activating factor , tumor necrosis factor and nitric oxide to the neutrophil influx and development of pulmonary haemorrhagic lesions following immune complex induced pneumonitis in rats and possible interactions between these mediators . increased levels of leukotriene B4 and tumor necrosis factor , measured by enzyme immunoassay and L 929 cytotoxicity assay , were found in the bronchoalveolar lavage 1 and 4 h after induction of the reaction , respectively , and their release was dependent on the previous generation of platelet activating factor . antagonism of leukotriene B4 receptors by RO 0254094 ( 2 ( 5 carboxypentyl ) oxy 6 6 3 , 4 dihydro 4 oxo 8 propyl 2H 1 benzopy ran 7 yl ) oxy hexyl benzenepropanoic acid ) , inhibition of nitric oxide synthesis by L NAME ( Nw nitro L arginine methyl ester ) and antagonism of PAF receptors by WEB 2170 ( 5 ( 2 chlorphenyl ) 3 4 dihydro 10 methyl 3 ( ( 4 morpholinyl ) carbony l ) 2 H , 7H cyclopenta ( 4 , 5 ) thieno ( 3 , 2 f ) ( 1 , 2 , 4 ) triazolo 4 , 3 , a ) 91 , 4 ) diazepine ) , significantly inhibited the intensity of haemorrhage , evaluated by the increased levels of extravascular hemoglobin in homogenates of …

Tumor necrosis factor induces enhanced responses to platelet activating factor and differentiation in human monocytic Mono Mac 6 cells. (1993 Apr)
tumor necrosis factor induces enhanced responses to platelet activating factor and differentiation in human monocytic Mono Mac 6 cells . human Mono Mac 6 cells exhibit characteristics of mature blood monocytes . treatment of these cells with human recombinant human tumor necrosis factor ( TNF ) resulted in an increase in phagocytosis and phorbol myristate acetate stimulated superoxide anion production at 12 h and growth retardation occurring at 24 h . moreover , TNF induced a moderate increase of CD14 surface antigen expression , used as a phenotypic marker of monocyte / macrophage differentiation . platelet activating factor ( PAF ) stimulated a rapid rise in cytosolic free Ca ( Ca i ) of 308 / 93 nM in TNF treated cells compared to untreated cells ( 33 / 8 nM , n 4 ) . The effect of TNF was dose and time dependent , evident after 12 h and maximal at 48 h . The enhanced PAF induced Ca i rise was inhibited by the PAF receptor antagonist L 659 , 989 and EGTA , indicating receptor dependent Ca influx . furthermore , L 659 , 989 and PAF inhibited specific 3H labeled PAF binding in TNF treated , but not in untreated cells . consistently , PAF stimulated arachidonic acid release only in TNF treated cells . preincubation of cells with anti TNF monoclonal antibodies abolished TNF induced effects , but failed to block lipopolysaccharide ( LPS ) effects . distinct mechanisms of action by LPS were …

Chemical and biochemical characterization of lignan analogs as novel PAF receptor antagonists. (1992 Jul)
chemical and biochemical characterization of lignan analogs as novel PAF receptor antagonists . various derivatives and isosteres of neolignans of the 2 , 5 diaryl tetrahydrofuran type have been synthesized as antagonists of platelet activating factor ( PAF ) . A detailed analysis of their structure activity relationship ( SAR ) has revealed a clear preference for an asymmetrical molecular configuration with a high degree of stereo and chiral specificity associated with greater potency . The trans 2S , 5S enantiomers are generally 10 200 times more potent in vitro than their corresponding cis or trans 2R , 5R isomers . A similar stereochemical preference is indicated by the recently reported PAF antagonist MK 287 which has undergone clinical evaluation . An azido derivative L 662 , 025 has been characterized as a photolabile irreversible antagonist of PAF for the investigation of solubilized and partially purified PAF binding proteins from cell membranes . The biological justification for concomitant inhibition of both PAF receptor and 5 lipoxygenase in inflammation is well recognized . The feasibility of developing such dual functional agents has been demonstrated by a group of dithiolane analogs of neolignans and several derivatives of futoenone .

Effect of inhaled platelet activating factor on bronchial inflammation in atopic non asthmatic subjects. (1993 Feb)
effect of inhaled platelet activating factor on bronchial inflammation in atopic non asthmatic subjects . We have investigated the effect of inhaled platelet activating factor ( PAF ) on bronchial mucosal inflammation in 6 atopic non asthmatic subjects in a double blind , placebo controlled , randomised and crossover study . On 2 study periods at least 4 weeks apart , fiberoptic bronchoscopy was performed 24 h after inhalation of either 200 micrograms PAF or methacholine ( control ) to obtain endobronchial biopsies . immunocytochemistry using antibodies for trypase ( AA1 ) and eosinophil cationic protein ( EG2 ) was performed to enumerate mast cells and eosinophils , respectively , in the bronchial submucosa . median values of AA1 cells and EG2 cells did not differ significantly after inhalation of PAF or control ( 23 . 8 vs . 39 and 6 vs . 8 / mm2 , respectively , PAF vs . control , non significant ) . Our findings suggest that within 24 h of inhaling a bronchoconstrictor dose of PAF , this agonist does not induce bronchial hyperresponsiveness or mucosal inflammation in atopic non asthmatic subjects . however , because of the small number of subjects studied , these preliminary data should be interpreted with caution .

Intracamerally injected platelet activating factor ( PAF ) induces marked intraocular inflammatory reactions. (1993 Feb)
intracamerally injected platelet activating factor ( PAF ) induces marked intraocular inflammatory reactions . An inflammatory response was elicited in the rabbit eye by intracameral injection of platelet activating factor ( PAF ) . PAF induced severe aqueous flare , corneal edema , pupillary constriction and marked biphasic changes in intraocular pressure ( IOP ) in a dose dependent manner . All of the responses to PAF were inhibited by the PAF receptor antagonist , BN 52021 ( 20 mg / kg , i . p . ) . The cyclooxygenase inhibitor , indomethacin ( 30 mg / kg , i . p . ) caused significant inhibition of the early phase PAF induced aqueous flare , pupillary constriction and intraocular hypertension , but did not effect PAF induced corneal edema or intraocular hypotension . NDGA ( 10 mg / kg , i . p . ) , a lipoxygenase inhibitor , did not inhibit the inflammatory effects of PAF . PAF induced chemotactic response was evaluated by tissue chemiluminescence . intracamerally injected PAF did not significantly increase chemiluminescence in cornea or iris ciliary body , but intracorneal injection of PAF did cause a chemotactic response in both the conjunctiva and cornea . these data suggest that PAF may be an important mediator of intraocular inflammation and that some PAF induced effects are prostaglandin dependent , while others may be independent of eicosanoid synthesis and release .

Platelet activating factor : a potent constrictor of cerebral arterioles in newborn pigs. (1988 Feb)
platelet activating factor : a potent constrictor of cerebral arterioles in newborn pigs . This study characterized the nature of the response to platelet activating factor ( PAF ) in the cerebral microcirculation of the newborn pig . Pial arterioles were observed directly using a closed cranial window in chloralose anesthetized piglets . topical application of 10 100 ng / ml PAF produced dose dependent decreases in pial arteriolar diameter ; diameters were 193 / 27 microns for control , 167 / 25 microns at 10 ng / ml , and 129 / 21 microns at 100 ng / ml . topical application of 30 300 ng / ml norepinephrine and 3 30 ng / ml u46619 , a purported thromboxane A2 receptor agonist , also produced dose dependent decreases in pial arteriolar diameter . after topical administration of u66985 ( 1 microgram / ml ) , a putative PAF antagonist , responses to PAF were attenuated significantly , but responses to norepinephrine and u46619 were unchanged . moreover , intravenously administered u66985 ( 0 . 1 mg / kg ) antagonized PAF responses as well . responses to PAF were unchanged after cyclooxygenase and leukotriene receptor inhibition . further , PAF did not increase cortical subarachnoid cerebrospinal fluid prostaglandin or leukotriene levels . these data indicate that PAF is a potent constrictor of cerebral arterioles in newborn pigs and that its mechanism of action is independent of formation of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism . these …

Effect of platelet activating factor with and without receptor antagonist ( web2170 ) on morphology of isolated cochlear outer hair … (2004 Mar)
effect of platelet activating factor with and without receptor antagonist ( web2170 ) on morphology of isolated cochlear outer hair cells . platelet activating factor ( PAF ) , generated from biologically active phospholipids , has been implicated as a potent inflammatory mediator and has been shown to be involved in many pathological processes , especially in inflammation and allergy . It has been suspected that PAF may be one of the inflammatory mediators in middle ear effusion that can induce sensorineural hearing loss , as observed in chronic otitis media . The PAF receptor antagonist web2170 has been studied extensively , and its inhibitory effects against various PAF actions are well proven in otologic systems . The purpose of our study was to determine the effect of superfusion of PAF and web2170 on morphological changes in isolated cochlear outer hair cells ( OHCs ) . isolated OHCs from adult chinchilla cochleas were exposed to albumin phosphate buffered saline solution ( 1 mg / mL ) , web2170 ( 5 mg / 30 mL ) , PAF ( 1 micromol / L ) , or both PAF ( I micromol / L ) and web2170 ( 5 mg / 30 mL ) . All experiments were performed at an osmolality of 305 / 5 mOsm at room temperature for 30 minutes . The cells were observed with an inverted microscope ; the images were stored and analyzed on the image Pro Plus program . The OHCs exposed to control albumin …

Differential actions of diacyl and alkylacylglycerols in priming phospholipase A2 , 5 lipoxygenase and acetyltransferase activation in human neutrophils. (1991 Aug)
differential actions of diacyl and alkylacylglycerols in priming phospholipase A2 , 5 lipoxygenase and acetyltransferase activation in human neutrophils . One aspect of human neutrophil ( PMN ) function during inflammation is formation of platelet activating factor ( PAF ) , leukotriene B4 ( LTB4 ) , and 5 hydroxyeicosatetraenoic acid ( 5 HETE ) , but production of these lipid mediators is limited if PMN are directly stimulated with soluble , physiologic agonists . In vitro , PMN activities can be enhanced by the process of primed stimulation where cells are sequentially treated with non stimulatory concentrations of different agonists . Many agents that prime PMN also induce production of 1 , 2 diacyl and 1 O alkyl 2 acylglycerols . therefore , we investigated whether diglycerides were involved in priming PMN for production of lipid mediators . We previously described the ability of the diacylglycerol , 1 oleoyl 2 acetylglycerol ( OAG ) , and its alkylacylglycerol analog , 1 O octadecenyl 2 acetylglycerol ( EAG ) , to prime phospholipase A2 ( PLA2 ) for subsequent activation by a second stimulus . however , while OAG also primed 5 lipoxygenase activity ( LTB4 and 5 HETE production ) , EAG priming inhibited LTB4 and 5 HETE formation . We now report the effects of diglyceride priming on acetyltransferase activation ( PAF formation ) . PMN , prelabeled with 1 O 9 , 10 3H hexadecyl 2 lyso sn glycero 3 phosphocholine , were primed with OAG or …

Ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet activating factor ( PAF acether ) … (1985 Aug)
ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet activating factor ( PAF acether ) to guinea pigs . bronchoconstriction and degenerative lesions of the bronchial epithelium were observed microscopically 1 min after the i . v . injection of 100 ng / kg of platelet activating factor ( PAF acether ) to the anaesthesized guinea pig . constricted arterioles containing marginated polymorphonuclear neutrophils and platelet aggregates were seen , as well as alveolar capillaries obstructed by thrombi formed by partially or totally degranulated platelets . three minutes after the injection of PAF acether , platelet diapedesis to the alveolar septa and lumen was clearly observed . bronchoconstriction was still present at 3 min , but subsided after 60 min , whereas oedema of the submucosa persisted accompanied by an infiltration of eosinophils and neutrophils . The infusion of prostacyclin prevented the formation of platelet aggregates and platelet diapedesis due to PAF acether , but the morphological evidence of bronchial constriction was not modified . aspirin failed completely to modify the effects of PAF acether . Our results show that PAF acether causes early formation and deposition of platelet aggregates , accompanied by the margination of polymorphonuclear neutrophil leucocytes in pulmonary vessels of the guinea pig . since bronchoconstriction persisted when platelet aggregation was inhibited with prostacyclin , aggregation by itself would not account for this effect . early platelet diapedesis in the vicinity of bronchial smooth muscle corroborates previous evidence that platelets contain and …

Platelet activating factor does not induce bronchial hyperreactivity in nonasthmatic subjects. (1993 Feb)
platelet activating factor does not induce bronchial hyperreactivity in nonasthmatic subjects . platelet activating factor ( PAF ) is a phospholipid which plays a role as a mediator in inflammation . recently , it has been implicated in the induction of bronchial hyperresponsiveness in man . In order to establish the effect of PAF on bronchial reactivity , 6 normal subjects without bronchial hyperresponsiveness inhaled 400 micrograms of PAF in 10 divided cumulative doses . All subjects felt a hot flush and a slight tracheal irritation after the inhalation of PAF . forced expiratory flows ( FEF ) were measured between each inhalation of PAF and did not change significantly . bronchial reactivity to methacholine ( MCH up to a dose of 2 mg ) was determined 1 , 7 , 14 and 21 days after inhalation of PAF . forced expiratory volume in 1 s ( FEV1 ) , forced expiratory flow between 25 and 75 , and at 75 of vital capacity ( fef25 75 and fef75 ) measured after the inhalation of 2 mg of MCH did not differ significantly from baseline values determined before PAF challenge . In conclusion , the administration of PAF by inhalation in tolerable doses does not induce bronchial hyperresponsiveness as determined by a reduction of 20 of FEV1 nor by more sensitive indicators of ventilatory obstruction , such as fef25 75 and fef75 .

Platelet activating factor primes endotoxin stimulated macrophage procoagulant activity. (1991 Jun)
platelet activating factor primes endotoxin stimulated macrophage procoagulant activity . macrophage procoagulant activity ( PCA ) at the site of inflammation may be induced by several stimuli including bacteria and endotoxin ( LPS ) . The local factors controlling PCA induction are poorly defined . The lipid mediator platelet activating factor ( PAF ) is ubiquitous to inflammatory sites . To determine the effect of PAF on LPS induced PCA , thioglycolate elicited murine peritoneal macrophages were exposed to PAF ( 10 ( 7 ) M ) or control medium for 30 min and then stimulated with LPS ( 10 micrograms / ml ) for 2 , 4 , or 6 hr . The ability of macrophages to shorten the clotting time of plasma ( ie . , PCA ) was then measured and clotting times were converted to PCA units using a thromboplastin standard . cytosolic calcium ( Ca2 i ) measurements were made using the calcium sensitive fluorescent dye indo 1 . PAF alone did not induce a rise in PCA expression ( medium alone , 47 / 11 mU / 10 ( 6 ) cells ; PAF alone , 49 / 12 mU / 10 ( 6 ) cells at t 4 hr ) , but PAF treatment prior to LPS exposure resulted in a significant increase in the LPS stimulated expression of PCA ( LPS alone , 190 / 29 mU / 10 ( 6 ) cells ; PAF / LPS , 329 / 57 mU …

Platelet activating factor induced functional changes in the guinea pig trachea in vitro. (1989 Oct)
platelet activating factor induced functional changes in the guinea pig trachea in vitro . The role of platelet activating factor ( PAF ) in airway hyperresponsiveness was investigated in guinea pigs challenged in vivo for 7 days , 10 min per day , with aerosolized PAF . tracheal smooth muscle strips set up in vitro for measuring isometric force exhibited increased sensitivity to histamine as compared to tissues from saline challenged control animals . No significant differences in the concentration response relationships in tissues from control and PAF treated animals were seen for acetylcholine or KCl . The threshold concentration of histamine to elicit contraction was 10 ( 7 ) M for control and 10 ( 10 ) M for the PAF treated tissues , and these changes persisted for several days following the last exposure to PAF . The histamine H2 receptor antagonist cimetidine , and the arachidonate cyclooxygenase inhibitor indomethacin potentiated histamine induced contractions in tissues from both the control and the PAF treated animals to similar magnitudes . intracellular microelectrode studies showed similar resting membrane potentials ( 51 mV ) and maximum depolarizations to the three agonists in the cells from control and PAF treated tissues . however , histamine depolarized the membrane greater in the range of 10 ( 7 ) 10 ( 5 ) M in the PAF treated tissues than in the controls . contractions to threshold concentrations of histamine were unaccompanied by any detectable changes in membrane potential . histological studies showed eosinophilic …

Calcium dependent PAF stimulated generation of reactive oxygen species in a human keratinocyte cell line. (1999 Jul)
calcium dependent PAF stimulated generation of reactive oxygen species in a human keratinocyte cell line . during inflammation and other pathological states , the lipid mediator platelet activating factor ( PAF ) and reactive oxygen species ( ROS ) are both generated . We have been investigating the effect of exogenous PAF on ROS formation in the human keratinocyte cell line ( hacat ) . ROS production , measured using luminol enhanced chemiluminescence ( CL ) , proved to be rapid , transient , PAF receptor mediated , and totally dependent on an increase in intracellular Ca2 ( Ca2 i ) and on the presence of extracellular Ca2 . repeated administration of PAF resulted in refractoriness to the agonist in terms of both capacities to increase Ca2 i and generate ROS . The cells , however , continued to respond fully to other stimulants ( bradykinin , epidermal growth factor , thapsigargin ) . The PAF induced increases in Ca2 i ( monitored using the fluorescent probe Fluo 3 ) were also rapid and transient and paralleled those of ROS generation . relatively specific inhibitors of potential ROS producing systems were administered in an attempt to characterize the ROS producing system ( s ) . inhibitors of xanthine oxidase , phospholipase A2 , lipoxygenase , cyclooxygenase and NO synthase did not interfere with PAF evoked ROS . The flavoprotein inhibitor diphenyleneiodonium and the mitochondrial cytochrome oxidase inhibitor KCN , prevented generation of ROS , making NAD ( P ) H …

Platelet activating factor and haematopoiesis. (1996 Sep)
platelet activating factor and haematopoiesis . XI . platelet activating factor has no effect on the production of interleukin 6 and tumor necrosis factor alpha by human bone marrow stromal cells . PAF is a phospholipid mediator of inflammation with stimulates IL 6 production by murine skin fibroblasts . although PAF is present in human bone marrow , its role in haematopoiesis is unknown . We have assessed whether PAF stimulates IL 6 and TNF alpha production by human bone marrow stromal cells ( mostly fibroblast like cells ) . We report that PAF ( 1 nM to 10 microm ) has no effect on the synthesis of IL 6 and TNF alpha by human bone marrow stromal cells . This difference may be due to the widely accepted concept tissue specific fibroblasts . The role of PAF in the regulation of human haematopoiesis remains to be elucidated .

Propofol inhibits human platelet aggregation induced by proinflammatory lipid mediators. (2004 Jul)
propofol inhibits human platelet aggregation induced by proinflammatory lipid mediators . lysophosphatidic acid ( LPA ) , platelet activating factor ( PAF ) , and thromboxane A ( 2 ) are proinflammatory lipid mediators that activate surface receptors on platelets , producing increased intracellular calcium , which is necessary for aggregation . We investigated propofol s effect on platelet aggregation and intracellular calcium mobilization caused by these three agonists . platelets from human volunteers were incubated in buffers containing LPA ( 1 microm ) , u46619 ( thromboxane A ( 2 ) analog ; 1 microm ) , or PAF ( 10 nM ) . propofol emulsion or 2 , 6 diisopropylphenol ( propofol without fat emulsion ) dissolved in ethanol was added to achieve concentrations of propofol used clinically : 5 or 10 microg / mL . after 2 min , aggregation or intracellular calcium concentrations were measured with optical techniques . propofol emulsion and propofol in ethanol produced similar inhibition of platelet aggregation induced by LPA , PAF , and u46619 in a dose dependent fashion . LPA , PAF , and u46619 each caused significant increases in intracellular calcium that were not modified by propofol . because propofol does not significantly alter intracellular calcium increases caused by receptor activation , inhibition appears to act distal to platelet receptors , inositol phosphate 3 , and phospholipase C . because the three lipid mediators play a key role in inflammation , their inhibition by propofol might be clinically important …

Intestinal NF kappab is activated , mainly as p50 homodimers , by platelet activating factor. (1998 Jul)
intestinal NF kappab is activated , mainly as p50 homodimers , by platelet activating factor . NF kappab , a transcription factor , upregulates gene transcription of many inflammatory mediators . Here , we examined the activity of NF kappab in the rat small intestine , and how it may be affected by platelet activating factor ( PAF ) , an important mediator for intestinal injury and inflammation . ileal nuclear extracts from sham operated and PAF ( 1 . 5 microg / kg ) injected rats were prepared for the assessment of NF kappab DNA binding activity , and the identification of NF kappab subunits . The experiment was also performed on neutrophil depleted rats to examine whether the PAF effect is neutrophil dependent . cellular NF kappab was localized by immunohistochemistry . We found that : ( a ) NF kappab is constitutively active in rat small intestine ; ( b ) PAF at a dose below that causing shock and bowel necrosis enhances DNA binding activity of NF kappab within 30 min after injection ; activated NF kappab contains predominantly p50 subunits ; ( c ) immunohistochemistry showed that PAF induced translocation of p50 into the nucleus of cells of the lamina propria , as well as of the epithelium ; and ( d ) the effect of PAF is abrogated by neutrophil depletion , suggesting a role of neutrophils in NF kappab activation . Our study suggests that NF kappab is weakly active constitutively in the …

Modulation of endotoxin induced inflammation in the bovine teat using antagonists / inhibitors to leukotrienes , platelet activating factor and … (1997 Sep)
modulation of endotoxin induced inflammation in the bovine teat using antagonists / inhibitors to leukotrienes , platelet activating factor and interleukin 1 beta . A leukotriene biosynthesis inhibitor ( mk886 ) , a platelet activating factor ( PAF ) receptor antagonist ( WEB 2086 ) , a recombinant human interleukin 1 receptor antagonist ( IL 1ra ) and a polyclonal antibody to recombinant bovine IL 1 beta ( anti rboil 1 beta ) was used to investigate the involvement of leukotrienes , PAF and IL 1 beta during endotoxin induced inflammation in the bovine teat cistern . endotoxin alone was infused into one teat cistern and endotoxin in combination with an inhibitor / antagonist was infused into another teat cistern of the same animal . Teat cistern samples were taken before infusion and at 3 . 5 and 7 h after infusion , and the numbers of neutrophils were counted . saline infusion was used as control . The inhibitors / antagonists were also tested in combination with leukotriene B4 ( LTB4 ) , PAF and rboil 1 beta , respectively . mk886 or WEB 2086 significantly reduced the accumulation of neutrophils mainly between 3 . 5 and 7 h after infusion , indicating roles for leukotrienes , probably LTB4 , and PAF in neutrophil accumulation during endotoxin induced inflammation . As WEB 2086 also reduced cell accumulation between 0 and 3 . 5 h , PAF was implicated also in the early influx of neutrophils . WEB 2086 almost …

Lymphatic smooth muscle responses to leukotrienes , histamine and platelet activating factor. (1988 Mar)
lymphatic smooth muscle responses to leukotrienes , histamine and platelet activating factor . regional lymphatics regulate the accumulation of edema resulting from inflammation . The effects of mediators of inflammation on lymphatic smooth muscle , the primary determinant of lymph flow , are poorly understood . We studied mesenteric lymphatic vessels in 22 anesthetized rats with in vivo videomicroscopy following topical applications of histamine , leukotriene C4 or D4 , or platelet activating factor ( PAF ) . diameter , contractility , and contraction frequency were measured , and flow was calculated . histamine caused increases in vessel diameter and contractility ( 174 and 218 of control , respectively ; P less than 0 . 05 ) , while contraction frequency was unaffected . leukotrienes C4 and D4 caused an increase in frequency of contraction ( 348 and 392 of control , respectively ; P less than 0 . 05 ) , while having no significant influence on diameter or contractility . PAF caused smooth muscle relaxation , resulting in vasodilation and a decrease in contraction frequency ( 202 and 5 of control , respectively ; P less than 0 . 05 ) . topical application of histamine and leukotrienes caused significant increases in calculated flow , while PAF decreased calculated flow . mediators of inflammation have striking and diverse effects on lymphatic smooth muscle activity .

Platelet activating factor receptor. (2002 May)
platelet activating factor receptor . platelet activating factor ( PAF ) is a pro inflammatory lipid mediator possessing a unique 1 O alkyl glycerophospholipid ( GPC ) backbone ( 1 O alkyl 2 acetyl sn glycero 3 phosphocholin ) . cloned PAF receptor , which belongs to the G protein coupled receptor superfamily , transduces pleiotropic functions including cell motility , smooth muscle contraction , and synthesis and release of mediators and cytokines via multiple heterotrimeric G proteins . pharmacological studies have suggested that PAF functions in a variety of settings including allergy , inflammation , neural functions , reproduction , and atherosclerosis . establishment of PAFR ( / ) mice confirmed that the PAF receptor is responsible for pro inflammatory responses , but that its roles in other settings remain to be clarified .

Increased hypodense eosinophils after activation with PAF acether and calcium ionophore in asthmatic subjects. (1996 Sep)
increased hypodense eosinophils after activation with PAF acether and calcium ionophore in asthmatic subjects . eosinophils play a major role in the pathogenesis of bronchial asthma . In this study , we examined the density characteristics of blood eosinophils from 9 normal healthy individuals and 9 allergic asthmatic patients . furthermore , the effect of platelet activating factor , a potent mediator of inflammation , and calcium ionophore , a23187 , on the density of normodense eosinophils ( density 1 . 085 g / ml ) has also been examined . initially , asthmatic patients had 27 . 0 / 1 . 1 eosinophils of lighter density ( density or 1 . 081 g / ml ) , significantly greater than that in the normal individuals ( 7 . 5 / 0 . 5 ) . after exposure to platelet activating factor ( 1 microm ) or calcium ionophore ( a23187 , 1 microgram / ml ) , the normodense eosinophils switched to hypodense in both groups : 16 . 7 / 2 . 1 and 54 . 2 / 3 . 7 , respectively , in normal individuals , and 30 . 6 / 5 . 7 and 77 . 4 / 2 . 3 , respectively , in asthmatic patients . these data demonstrated that a certain percentage of normodense eosinophils from asthmatics and normal subjects switched to hypodense after activation with platelet activating factor or calcium ionophore . furthermore , eosinophils from asthmatics switched to a greater …