Responses of rat nasal epithelium to short- and long-term exposures of ozone: image analysis of epithelial injury, adaptation and repair

This article reviews the use of computerized image analysis and standard morphologic techniques to characterize the responses of nasal epithelium in laboratory rats to single or repeated exposures to a common urban air-pollutant, ozone. Alterations in the number and composition of the epithelial cell populations after either short- or long-term exposures are described. The principal nasal epithelial alteration induced by repeated exposures to this irritating, oxidant pollutant is mucous cell metaplasia (i.e., transformation of airway epithelium, normally devoid of mucous cells, to a secretory epithelium containing numerous mucus-secreting cells). This metaplastic change, induced by acute or chronic ozone exposures, has been morphometrically examined at various times post-exposure. In this article, we describe our current understanding of the pathogenesis and persistence of ozone-induced mucous cell metaplasia in nasal epithelium based on the results of these morphometric studies.     

Face scanning and responsiveness to social cues in infant rhesus monkeys.

Investigated the development of gaze aversion in 8 infant rhesus monkeys (Macaca mulatta) by recording their visual fixations while they scanned pictures of monkey faces looking back at them and pictures of monkey faces looking away. During the 1st week of life, Ss inspected the 2 face-types equally. During Weeks 3 and 7, however, they inspected the faces looking back less than the faces looking away. The maturation of selective viewing was not paralleled by changes in scanning strategies (e.g., by a shift from scanning the contours of faces to fixations of internal details). The implications of early species-typical social awareness for social and perceptual development in rhesus monkeys are discussed. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationships of PPARgamma and PPARgamma2 mRNA levels to obesity, diabetes and hyperinsulinaemia in rhesus monkeys

OBJECTIVE: To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) together with CCAAT/enhancer binding protein alpha (C/EBPalpha), lipoprotein lipase (LPL) and glucose transporter (GLUT4) mRNA in adipose tissue of rhesus monkeys in relation to obesity. DESIGN: Cloning of the PPARgamma1 and gamma2 cDNAs and analysis of PPARgamma, C/EBPalpha, LPL and GLUT4 mRNA levels in the adipose tissue of lean and obese monkeys. SUBJECTS: 28 rhesus monkeys (Macaca mulatta) with a wide range of body weights (9.2-22.6 kg) and with or without type 2 diabetes. MEASUREMENTS: Sequence of PPARgamma1 and gamma2. Tissue distribution of PPARgamma1 and gamma2. The mRNA levels of PPARgamma, C/EBPalpha, LPL and GLUT4 in adipose tissue. The ratio of PPARgamma2 mRNA to total PPARgamma mRNA. RESULTS: The monkey PPARgamma2 protein showed 99% identity with the human protein. PPARgamma1 mRNA was shown to be expressed in various tissues and most abundantly in adipose tissue. PPARgamma2 existed mainly in adipose tissue. A significant correlation between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and obesity was observed, whereas total PPARgamma mRNA levels showed no significant relationships to obesity. There was also a significant relationship between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and fasting plasma insulin concentration. The mRNA levels of C/EBPalpha, LPL and GLUT4 were highly correlated to that of total PPARgamma mRNA. They were also significantly correlated to the mRNA levels of PPARgamma1 and PPARgamma2. CONCLUSIONS: The ratio of PPARgamma2 mRNA to total PPARgamma mRNA is related to obesity in the rhesus monkey and mRNA expression of PPARgamma1, PPARgamma2, C/EBPalpha, LPL and GLUT4 appear to be coordinated in vivo.     

Fetal and maternal endocrine responses to experimental intrauterine infection in rhesus monkeys

OBJECTIVE: Our purpose was to describe the temporal and quantitative relationships among intrauterine infection, fetal-placental steroid biosynthesis, and preterm labor in a nonhuman primate model. STUDY DESIGN: On approximately day 130 of gestation (term 167 days) chronically instrumented rhesus monkeys (Macaca mulatta) were infected with 10(6) colony-forming units of group B streptococci either by intraamniotic (n = 4) or choriodecidual (n = 2) inoculation. As controls, four additionally chronically instrumented noninfected monkeys were followed up to spontaneous parturition. Amniotic fluid and maternal and fetal arterial blood were serially sampled in all monkeys (both before and after infection) for progesterone, estrone, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and cortisol by specific radioimmunoassays, and uterine activity was continuously recorded. RESULTS: Spontaneous parturition was preceded by gradual and significant increases in the plasma concentrations of fetal dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione and fetal and maternal levels of estrone, estradiol, and progesterone but not by changes in cortisol. In contrast, infection-associated parturition (either intraamniotic or choriodecidual) was characterized by abrupt increases in fetal dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, progesterone, and cortisol but not by increases in maternal or fetal estrone or estradiol. Infection-associated steroid changes occurred concurrently with or after increases in uterine activity. CONCLUSION: Infection-associated preterm parturition is associated with dramatic increases in fetal adrenal steroid biosynthesis but not by corresponding increases in placental estrogen biosynthesis. This suggests that fetal stress in accompanied by placental dysfunction and that infection-associated parturition is not dependent on the increased estrogen biosynthesis observed in spontaneous parturition.     

Effects of clonidine, dexmedetomidine and xylazine on thermal antinociception in rhesus monkeys

The antinociceptive effects of the s.c. administration of the alpha-2 agonists clonidine (0.0032-1.0 mg/kg), dexmedetomidine (0.001-0.032 mg/kg) and xylazine (0.1-3.2 mg/kg) were examined in the warm-water tail withdrawal assay in rhesus monkeys. The three agonists were dose-dependently effective in this assay; their potency order being dexmedetomidine > clonidine > xylazine. The alpha-2 antagonist idazoxan (0.1-3.2 mg/kg) caused dose-dependent and roughly parallel rightward shifts in the dose-effect curves for the three agonists. Apparent pA2 analysis with idazoxan yielded homogeneous values for the three agonists, supporting the notion that similar receptors mediate their antinociceptive effects. The opioid antagonist quadazocine (1.0 mg/kg) did not antagonize the antinociceptive effects of clonidine and xylazine, indicating that opioid receptors do not participate in the effects of the compounds in this assay. At dose ranges found to be effective in the antinociceptive assay, clonidine, dexmedetomidine and xylazine also dose-dependently caused sedation, muscle relaxation, bradycardia and moderate respiratory depression. The sedative, muscle relaxant and respiratory depressant effects of xylazine could be antagonized by idazoxan, suggesting that these effects may be mediated through alpha-2 receptors. These data indicate that the three imidazoline alpha-2 agonists, clonidine, dexmedetomidine and xylazine are effective s.c. in the warm-water tail withdrawal assay in rhesus monkeys, but only at doses that produce other behavioral and physiological effects.     

Hormonal control of female sexual attractiveness proceptivity, and receptivity in rhesus monkeys

Microsurgical exploration of 15 adults with Arnold-Chiari malformation with and without hydromyelia using 3 to 20 X magnification has led to the following conclusions. Hydromyelia, associated with Arnold-Chiari malformation, is a progressive mechanical disorder that causes spinal cord deficits by pressure distention of the cord. Arnold-Chiari malformation causes slowly or suddenly progressive bulbar dysfunction by impaction of the malformation in the foramen magnum. Decompression of both can be achieved by a suboccipital carniectomy, upper cervical laminectomy, establishing an outlet from the fourth ventricle, and opening the distended cord in the thinnest exposed area, which is usually along the dorsal root entry zone. If Pantopaque myelography in patients in the supine position shows the Arnold-Chiari malformation, hydromyelia can be established as a cause of central cord deficit even if myelography shows the cord size to be normal. Syringomyelia, traditionally considered a degenerative disease, is a less common cause of a slowly progressive central cord deficit than either hydromyelia or intramedullary tumor.     

Behavioral and hormonal responses to separation in infant rhesus monkeys and mothers.

Examined the effects of social stimuli on behavioral and physiological responses in 9 infant rhesus monkeys, 8 Ss at 4–6 mo (Exp I) and 7 of the original Ss and an additional S at age 8–10 mo (Exp II). Infants and mothers were removed from the social group and housed as dyads. Following this period, infants were removed and separated under 4 counterbalanced conditions: (a) totally isolated—placed in a holding cage for 24 hrs; (b) mother present, no contact—housed in a single cage in view of their mother, no contact; (c) mother present, contact—similar to above, with mother in proximity to the infant; and (d) peer present—separated but in proximity to a peer. In Exp I, infants rarely vocalized when totally isolated but showed high rates of vocalization in the presence of the mother, both with and without contact. In the mother-present conditions, they failed to show a plasma cortisol response. In contrast, totally isolated infants showed a significant elevation in plasma cortisol. In Exp II, these infants were separated for 3 days under 2 conditions: mother present and totally isolated. Results support and extend the findings of Exp I, indicating that age was not a factor in modulating response to separation. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between glomerular epithelial cell injury and proteinuria in IgA nephropathy

The cost of in-hospital percutaneous transluminal coronary angioplasty (PTCA) has risen since the introduction of the coronary stent. Increased attention is now being given to the PTCA charges in Japan and a multicenter study is necessary with regard to in-hospital charges. To clarify the differences in in-hospital charges for PTCA with and without coronary stent [Stent Group and plain old balloon angioplasty (POBA) Group, respectively], we studied the PTCA charges of 352 patients in 6 hospitals. Age, male gender and extent of coronary artery disease were not different. The ratio of acute myocardial infarction ranged from 16% to 64% and that of coronary stenting ranged from 24% to 65% (p < 0.001). In-hospital charge ranged from 1.4 +/- 0.8 to 2.2 +/- 1.0 million yen (p < 0.0001). The procedural charge accounted for 53% to 75% of the in-hospital charge (p < 0.01). The in-hospital charge ranged from 1.6 +/- 0.7 to 3.3 +/- 1.6 million yen in the Stent Group, higher than the charge of 1.1 +/- 0.8 to 1.9 +/- 0.7 million yen in the POBA Group (p < 0.0001). There was a statistical difference in the number of balloon catheters used (1.1 +/- 0.4 to 2.1 +/- 0.9, p < 0.005) but not in the mean number of stents used (1.1 +/- 0.3 to 1.4 +/- 0.7). The procedural charge of the institutes with higher stenting rate (> 45%) seemed to be lower than that of the institutes with lower stenting rate (p < 0.02). In conclusion, there are large variation between institutions in PTCA charges, and in-hospital charges increased with the use of stents on introduction of the Diagnosis Related Group used in the United States. We should charge separately for coronary stenting and POBA. Despite any initial increase in the in-hospital charge for coronary stenting compared to POBA, successful stent implantation will result in a superior saving in procedural charges.     

Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits

Oxygen tension was measured using flexible polarographic microelectrodes within the oviductal and uterine lumen in rhesus monkeys (n = 9), golden hamsters (n = 21) and rabbits (n = 6), during the reproductive cycle (monkey), during oestrus and pseudopregnancy (hamsters, rabbits) and during pregnancy (hamsters). In general, oxygen tensions in each species were much less than half of atmospheric O2, ranging from high values of about 60 mm Hg (8.7% O2) in the rabbit oviduct, rabbit and hamster uterus, to as low as 11 mm Hg (1.5% O2) in the monkey uterus. Oxygen tensions did not vary significantly between left and right sides of the reproductive tracts (all species), nor between pregnant and pseudopregnant states nor between oviduct and uterus (hamsters). Differences owing to reproductive stage were found in the monkey oviduct, hamster oviduct and uterus, and rabbit uterus. Oxygen tensions were consistently very low (11-14 mm Hg) in the monkey uterus throughout the menstrual cycle. In hamsters and rabbits, intrauterine O2 decreased significantly at about the normal time of blastocyst formation and implantation, to 37 mm Hg (5.3% O2) and 24 mm Hg (3.5% O2), respectively. This study indicates that embryos develop in vivo under low oxygen concentrations, especially during the peri-implantation period. The data have implications for investigations of embryo metabolism and for improving embryo development in vitro.     

Effects of age, objects, and visual experience on affective responses of rhesus monkeys to strangers.

Studied the development of lipsmacking and grimacing, facial expressions associated with friendliness and fear, respectively, in 26 rhesus monkeys raised under 3 conditions that included visual exposure to (a) monkeys and people, (b) one monkey, (c) neither monkeys nor people. Ss were tested through Life Weeks 1–22 for responses to their mirror image or a human face. Age, stimulus configuration, and experience interacted in the development of the 2 responses. Lipsmacking generally occurred earlier than grimacing and was most frequently elicited by the face. Frequency of lipsmacking increased initially, then declined; in contrast, frequency of grimacing increased progressively throughout testing. Rearing conditions significantly affected age of first response, level of responsiveness, and stimulus differentiation. The most restricted group was oldest at first response, least responsive, and showed the weakest differentiation of stimuli; the most experienced group was at the opposite extreme on these comparisons. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Generation of reactive oxygen species by blood monocytes during acute Plasmodium knowlesi infection in rhesus monkeys

The status and kinetics of monocyte activation during acute P. knowlesi infection was investigated by latex-induced, luminol-dependent chemiluminescence (CL) response. The contribution of various reactive oxygen species (ROS) to CL response was estimated before infection and at peak parasitaemia (day 7 post infection) by using scavengers of ROS (benzoate, catalase and superoxide dismutase). The chemiluminescence index (CLI) was not found to be significantly different from controls on day 2 postinfection, but was significantly higher on days 5 and 7 postinfection. Hydroxyl radical (OH.) production was considerably elevated, whereas superoxide anion (O2-.) and hydrogen peroxide (H2O2) production dropped following infection. These changes in generation of ROS are discussed in relation to the progression of parasitaemia to high levels, immunopathology and immunosuppression during acute P. knowlesi infection.     

Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma

The anti-asthmatic effects of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 microg x day(-1). The trial was designed as a randomized, double-blind, parallel-group study in several European countries. Sixty nine patients were treated for 6 weeks with theophylline plus BDP 400 microg x day(-1), compared to 64 patients treated with BDP 800 micro x day(-1). The mean+/-SD serum theophylline concentration was 10.1+/-4.2 mg x L(-1). Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p<0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p<0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 microg x day(-1) and beclomethasone dipropionate 800 microg x day(-1) in patients whose asthma is not controlled on beclomethasone dipropionate 400 microg x day(-1). The results support the use of theophylline as a steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.     

Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma

The anti-asthmatic effect of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 micrograms/day. The trial was designed as a randomized, double-blind, parallel-group study in several European countries. 69 patients were treated for 6 weeks with theophylline plus BDP 400 micrograms/day, compared to 64 patients treated with BDP 800 micrograms/day. The mean +/- SD serum theophylline concentration was 10.1 +/- 4.2 mg/l. Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow rate (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p < 0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p < 0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 micrograms/day and beclomethasone dipropionate 800 micrograms/day in patients whose asthma is not controlled on beclomethasone dipropionate 400 micrograms/d. The results support the use of theophylline as steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.     

Biotransformation and hepatotoxicity of HCFC-123 in the guinea pig: potentiation of hepatic injury by prior glutathione depletion

The chlorofluorocarbon substitute 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) is a structural analog of halothane. Both are oxidatively metabolized by CYP2EI, producing a reactive trifluoroacyl acid chloride intermediate and have been shown to cause acute liver necrosis in the guinea pig. With halothane, liver injury has been associated with the degree of reactive intermediate binding to hepatic protein. This injury can be potentiated by prior glutathione (GSH) depletion. Thus, the combination of GSH depletion and HCFC-123 exposure was evaluated for its hepatotoxic potential in this species. Male outbred Hartley guinea pigs were injected with either 0.8 g/kg l-buthionine-(S,R)-sulfoximine (BSO) to deplete hepatic glutathione or vehicle control solution 24 hr before a 4-hr inhalation exposure to 1.0% (v/v) HCFC-123 with 40% O2. HCFC-123 caused minimal liver injury with only 1 of 8 exposed animals displaying confluent zone 3 necrosis. GSH depletion potentiated injury producing submassive to massive liver necrosis in some animals. This potentiation was associated with a 36% increase in covalent binding of reactive HCFC-123 intermediates to hepatic protein. These results were not due to alterations in the biotransformation of HCFC-123 as indicated by plasma concentrations of the metabolites trifluoroacetic acid and fluoride ion which were not affected by BSO pretreatment. HCFC-123 was also found to cause a decrease in liver GSH concentrations following exposure. These findings demonstrate a role for hepatic GSH in helping to prevent covalent binding by the trifluoroacyl acid chloride intermediate. Inhalation of HCFC-123 can cause acute hepatic injury in the guinea pig that is worsened by low hepatic GSH concentrations.     

Observational conditioning of fear to fear-relevant versus fear-irrelevant stimuli in rhesus monkeys.

Two experiments examined whether superior observational conditioning of fear occurs in observer rhesus monkeys that watch model monkeys exhibit an intense fear of fear-relevant, as compared with fear-irrelevant, stimuli. In both experiments, videotapes of model monkeys behaving fearfully were spliced so that it appeared that the models were reacting fearfully either to fear-relevant stimuli (toy snakes or a toy crocodile), or to fear-irrelevant stimuli (flowers or a toy rabbit). Observer groups watched one of four kinds of videotapes for 12 sessions. Results indicated that observers acquired a fear of fear-relevant stimuli (toy snakes and toy crocodile), but not of fear-irrelevant stimuli (flowers and toy rabbit). Implications of the present results for the preparedness theory of phobias are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs

Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. We studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial beta-adrenergic blockade (propranolol, 0.15 mg/kg i.v.) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa (from 19.8 +/- 6.1 to 28.3 +/- 8.7 mmHg, P < 0.01) and calculated PVR (from 437 +/- 139 to 720 +/- 264 dyn.s.cm-5, P < 0.01), both of which decreased with 17 ppm NO. ALI decreased arterial PO2 and increased airway pressure, shunt, and dead space ventilation. Ppa (19.8 +/- 6.1 vs. 23.4 +/- 7.7 mmHg) and PVR (437 +/- 139 vs. 695 +/- 359 dyn.s.cm-5, P < 0.05) were greater during ALI than during hyperoxia. No inhalation had no measureable effect during ALI before or after beta-adrenergic blockade. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 micrograms) induced an immediate decrease in Ppa and PVR during ALI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response to inhaled nitric oxide in acute lung injury depends on distribution of pulmonary blood flow prior to its administration

Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced by improvements in oxygenation, are variable. We hypothesized that the effect of iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In the present study we evaluated the effect of iNO on PBF in normal healthy dogs and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n = 5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA" (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before giving the same dose of OA. Measurements of regional PBF and lung water concentration (LWC) using positron emission tomography (PET) and H215O were performed before and after OA or placebo, and then again at concentrations of 10, 40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these animals, PBF redistributed from the dorsal edematous regions of the lungs to the nondependent zones, thus partially preserving normal ventilation/ perfusion relationships. As in the normal animals, in Group OA only, iNO did not significantly change either PBF or oxygenation. In Group E+OA, the administration of low-dose endotoxin eliminated perfusion redistribution from the dorsal edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53 mm Hg, a decrease that was significantly greater than that in Group OA only. In Group E+OA, administration of iNO restored perfusion redistribution to a similar level as in Group OA only, which was associated with a significant improvement in PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40 ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on the pre-iNO perfusion pattern, which may help explain the variable response to iNO often observed in patients with acute respiratory distress syndrome.     

Properties of soluble and membrane intestinal hydrolases in Macaca rhesus monkeys

Evidence from several central nervous system (CNS) inflammatory disease models suggests that intrathecal complement synthesis may contribute to early inflammatory events in the brain. In this study, we examined the expression of the receptor for C5a (C5aR), a potent inflammatory and chemotactic factor, in the brains of transgenic mice with constitutive astrocyte expression of interleukin-3 (IL-3), a hematopoietic and immunomodulatory cytokine. By in situ hybridization, we demonstrated that cells infiltrating the cerebellar meninges, the cerebellum, and demyelinating lesions in the cerebellum were strongly positive for C5aR mRNA. By immunohistochemistry, the infiltrating cells expressing the C5aR were identified as macrophages based on staining with antibodies to the complement receptor type 3 and F4/80, a mouse macrophage-specific marker. In addition, some of the cells in cerebellar lesions were positive for the astrocyte-specific marker, glial fibrillary acidic protein, suggesting that a subpopulation of astrocytes in these lesions express elevated levels of the C5aR. Increased C5aR expression was also observed in cortical neurons in the occipital cortex and in pyramidal neurons in the cornu ammonis and subiculum of the hippocampus, at both the protein and mRNA levels. These data suggest that IL-3 may play an immunomodulatory role in C5aR expression on several cell types in the brain and that increased C5aR expression correlates with the pathology seen in this model. The transgenic mice used in this study provide a useful tool for characterizing the mechanism of regulation of the C5aR expression and for examining the functions of this chemotactic receptor in CNS inflammation.