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PubMed1988

Defective chemotaxis of human alveolar macrophages.

Human pulmonary alveolar macrophages (PAM) from normal subjects, unlike peripheral blood monocytes (PBM), are unable to migrate in response to various chemoattractants, such as C5a,f-Met-Leu-Phe (fMLP) and phorbol myristate acetate (PMA). Inflammatory PAM obtained from sarcoid patients also failed to exhibit a chemotactic response. Binding studies using [3H]PDBU demonstrate high affinity receptors for phorbol esters on PAM surface, in a comparable amount (1.5-2.4 X 10(6) receptors/cell) to PBM (8-15 X 10(5) receptors/cell). Moreover, PAM were comparable to PBM in terms of superoxide anion (O2-) release in response to PMA. Therefore, the defective locomotory response of PAM cannot be accounted for by lack of chemoattractant receptors, at least for phorbol esters. Worthy of note, PMA receptors on PAM are able to transduce activating signals for O2- generation. These findings show that competence for chemotaxis is heterogeneously distributed among mononuclear phagocytes.

Antigens, Surface↗

PubMed1985

Retinal acuity evaluation with the potential acuity meter in glaucoma patients.

The potential acuity meter (PAM) is designed to evaluate retinal acuity in the presence of media opacities. We looked at patients with glaucoma but with clear media, and compared best corrected visual acuity with PAM results to see if they produced comparable results. Sixty eyes in 38 glaucoma patients and 20 eyes in 10 normal ocular patients were evaluated. Our results indicate that PAM visual acuity is a reliable indicator of Snellen visual acuity in normal eyes, in eyes with mild to moderate glaucomatous damage, and when PAM visual acuity measurements were better than 20/60. However, when visual field loss is severe and when PAM visual acuity readings were worse than 20/60, the correspondence between these and Snellen visual acuity was erratic. Poor PAM results will not correlate with postoperative visual acuity in patients with advanced glaucoma and cataracts.

Glaucoma↗

PubMed1999

A cycloplatinated compound of p-isopropylbenzaldehyde thiosemicarbazone and its chloro-bridged derivative induce apoptosis in cis-DDP resistant cells which overexpress the H-ras oncogene.

cis-Diamminedichloroplatinum(II) (cis-DDP) is a widely used antitumour drug which produces important damage on the DNA inducing apoptosis in several cell lines. We have analyzed the cytotoxic activity of novel cyclometallated complexes of p-isopropylbenzaldehyde thiosemicarbazone (p-is.TSCN) and their dimeric chloro-bridged derivatives in murine keratinocytes transformed by the H-ras oncogene which are resistant to cis-DDP (Pam-ras cells). The data show that, in contrast with cis-DDP, the tetrameric cycloplatinated complex [Pt(p-is.TSCN)]4 and its dimeric chloro-bridged derivative [Pt(microCl)(p-is.TSCN)]2 have a good in vitro therapeutic index when comparing the cytotoxicity in Pam-ras cells to normal murine keratinocytes (Pam 212 cells) since they induce cell death in Pam-ras cells at drug concentrations significantly lower than those needed to kill Pam 212 cells. At equitoxic doses (IC90), both complexes produce characteristic features of apoptosis in Pam-ras cells together with a drastic decrease in levels of H-ras protein. These effects are not observed when the cells are treated with the IC90 of the cis-DDP drug nor the p-is.TSCN ligand. Altogether, these results suggest that the platinum compounds [Pt(p-is.TSCN)]4 and [Pt(microCl)(p-is.TSCN)]2 might have potential as antitumour agents in view of their specific induction of apoptosis in cis-DDP resistant cells.

Animals↗

PubMed2000

Neuropeptide amidation: cloning of a bifunctional alpha-amidating enzyme from Aplysia.

One of the most common mechanisms of posttranslational modifications to generate biologically active (neuro)peptides is the process of peptide alpha-amidation. The only enzyme known to catalyze this important modification is peptidylglycine alpha-amidating monooxygenase (PAM): a (bifunctional) zymogen, giving rise to a monooxygenase (PHM) and a lyase (PAL). The highly peptidergic central nervous system and endocrine system of the marine mollusk Aplysia has homologs of various mammalian peptide processing enzymes, including furin, Afurin2, prohormone convertase 1 (PC1), PC2, carboxypeptidase E (CPE) and CPD. Previously, it has been shown that the abdominal ganglion of Aplysia, which contains approximately 800 peptidergic bag cell neurons, contains the highest specific alpha-amidating activity. We have identified and cloned multiple overlapping central nervous system and bag cell cDNAs that encode a predicted 748-residue protein that is a member of the PAM family. The protein sequence contains the contiguous sequence of the catalytic domains of PHM and PAL, clearly demonstrating the existence of bifunctional Aplysia PAM, the first invertebrate PAM zymogen with an organization similar to that in vertebrates. None of the characterized clones encoded the so-called exon A domain between the PHM and PAL domains. Furthermore, in a specific search by reverse transcription-polymerase chain reaction of RNA from multiple tissues we could only detect exon A-less transcripts. PAM expression was detected in the central nervous system, and in several endocrine and exocrine organs. Aplysia PAM is a candidate prohormone processing enzyme that plays an important role in the processing of Aplysia prohormones in the secretory pathway.

Amino Acid Sequence↗

PubMed2003

Direct voltammetry and electrochemical catalysis with horseradish peroxidase in polyacrylamide hydrogel films.

This paper reports the direct voltammetry of horseradish peroxidase (HRP) incorporated in amphiphilic polyacrylamide (PAM) films modified on pyrolytic graphite (PG) electrodes. Cyclic voltammetry of HRP-PAM films showed a pair of well-defined, nearly reversible peaks at approximately -0.33 V vs. SCE in pH 7.0 buffers, characteristic of HRP heme Fe(III)/Fe(II) redox couple. The PAM films in solution contained large amounts of water and formed a hydrogel, and provided a favorable microenvironment for HRP and facilitated its direct electron transfer with underlying PG electrodes. The apparent heterogeneous electron transfer rate constant (k(s)) and formal potential (E*') were estimated by fitting the data of square wave voltammetry (SWV) with the non-linear regression analysis. UV-vis absorption spectra demonstrated that HRP in PAM films retained its secondary structure similar to its native state. The embedded HRP in PAM films showed the electrocatalytic activity to various substrates such as nitrite, oxygen and hydrogen peroxide. The possible mechanism of catalytic reaction of H(2)O(2) with HRP-PAM films was proposed.

Acrylic Resins↗

PubMedDate not supplied

Functional activities of alveolar macrophages in rat exposed to hyperoxia (normobaric O2).

Pulmonary alveolar macrophages (PAM) from rats exposed to 100% normobaric oxygen for 24, 48 and 65 h were collected by bronchoalveolar lavage. The cell yield was not modified by a 24 h exposure, but after 48 h, the number of PAM decreased and polymorphonuclear leucocytes were found in the lavage liquid. These modifications were amplified after a 65-h exposure. The percentage of uptake of Staphylococcus aureus after 30 min of incubation with PAM from rats exposed for 24 h and 48 was unchanged. No impairment of intracellular bactericidal activity toward S. aureus could be demonstrated in PAM from rats exposed to O2 for 24 h. After 48 h of O2 exposure, a slightly significant decrease in intracellular bactericidal activity was found only after 120 min of incubation. Nitroblue tetrazolium reduction and chemiluminescence were measured in PAM from O2-exposed and control rats: no modification could be demonstrated after 24 and 48 h of exposure. These results suggest that the PAM is relatively resistant to oxygen toxicity.

Animals↗

PubMed2000

Potential acuity meter accuracy in cataract patients.

PURPOSE: To determine potential acuity meter (PAM) accuracy in patients with cataract as the only ocular disease. SETTING: Hospital de Clínicas de Porto Alegre, Brazil. METHODS: This prospective study comprised 74 eyes with cataract. Patients with other ocular pathology diagnosed before or after surgery, as well as those with complicated surgeries, were excluded. All patients had PAM evaluation before surgery; these results were compared to the final postoperative visual acuity. Patients were divided into 4 cataract groups based on the Lens Opacity Classification System II: Group 1, early cataracts (nuclear opalescence [NO] 1 and/or posterior subcapsular cataracts [P] 1 and/or cortical opacity [C] < 2); Group 2, definite cataracts (NO2 and/or C2, with or without P1); Group 3, posterior cataracts (P2 or P3); Group 4, mature cataracts (N3 and/or C > or = 3, with or without P1). The PAM result was considered accurate if it was within 2 lines of the postoperative best spectacle-corrected visual acuity (BSCVA) 3 months after surgery. RESULTS: All patients had a BSCVA of 20/20. Accuracy of the PAM was 58.3% in Group 1, 50.0% in Group 2, 27.8% in Group 3, and 6.7% in Group 4 (P =.000 017). Patient age did not influence the results. CONCLUSIONS: The PAM may be used as a complementary tool in evaluating early and nondense cataracts; however, patients should not be excluded as candidates for cataract surgery based solely on PAM results.

Cataract↗

PubMed2002

Accuracy of IRAS GT interferometer and potential acuity meter prediction of visual acuity after phacoemulsification: prospective comparative study.

PURPOSE: To assess and compare the accuracy of 2 methods of predicting visual acuity after phacoemulsification. SETTING: Department of Ophthalmology, Montpellier, France. METHODS: This prospective study evaluated 47 eyes of 47 patients having uneventful phacoemulsification over a 1-month period. All the patients had mild to moderate cataract. Visual acuity recovery was predicted using the white-light IRAS GT interferometer on the 3- and 8-degree wide test area and the Guyton-Minkowski potential acuity meter (PAM). Best corrected visual acuity was evaluated 1 day before and 1 month after surgery. RESULTS: Both the interferometer and PAM underestimated the retinal visual capacity. Three-degree white-light interferometry gave significantly better mean predicted results than 8-degree interferometry and the PAM. There was no statistically significant disparity between predicted and postoperative results with 3-degree interferometry (1.04 +/- 0.57 logMAR; -0.09 +/- 0.27 decimal) (P =.0647) and a statistically significant disparity with 8-degree interferometry (0.89 +/- 0.59 logMAR; -0.13 +/- 0.27 decimal) and the PAM (0.66 +/- 0.62 logMAR; -0.22 +/- 0.24 decimal) (P =.0001). The predicted values were widely dispersed; the correlation indices were 0.38 with the PAM (P =.091), 0.39 with 3-degree interferometry (P =.001), and 0.49 with 8-degree interferometry (P =.0005). CONCLUSIONS: Three-degree white-light interferometry gave more accurate results than 8-degree interferometry and the PAM. The wide dispersion of results and unsatisfactory correlation indices show the tests are poor predictors of individual acuity. They should be used semiquantitatively and the results interpreted in relation to the clinical data. Qualitative methods may be useful in confirming or refuting visual recovery capacity ascertained by quantitative systems.

Adult↗

PubMed2002

Plasticity in hippocampal peptidergic systems induced by repeated electroconvulsive shock.

The regulated secretion of bioactive peptides requires the coordinated actions of a variety of gene products ranging from peptide precursors to post-translational processing enzymes and the cytosolic machinery involved in vesicle exocytosis. To evaluate the role of plasticity of peptidergic processes in the clinical response to electroconvulsive treatment, we monitored expression of a peptide (neuropeptide Y, NPY), a post-translational processing enzyme (peptidylglycine alpha-amidating monooxygenase, PAM) and a cytosolic component involved in peptide secretion and neurite extension (kalirin) in the hippocampus. Adult male rats were subjected to single or repeated electroconvulsive shock. In general, levels of NPY, PAM and kalirin mRNA showed similar transient increases after acute and repeated electroconvulsive shock. In contrast, repeated, but not acute, electroconvulsive shock brought about widespread changes in protein expression. Increased amounts of NPY and PAM accumulated in mossy fibers, and dentate granule cell dendrites contained increased amounts of NPY, PAM and kalirin. CA1 pyramidal neurons expressed increased amounts of PAM and kalirin, with an accumulation of both proteins in their dendrites. Scattered interneurons contained increased levels of NPY and PAM after acute and repeated shocks. However, scattered interneurons contained increased levels of kalirin only after repeated shocks. The distinctly different effects of repeated vs. acute electroconvulsive shock support an important role for peptidergic plasticity in the therapeutic effects observed following electroconvulsive treatment.

Animals↗

PubMed2026

Structure-Function Analysis of the Benzyloxy Moiety of the Delta-Opioid Receptor Positive Modulator BMS-986187: Identification of a Derivative with High Selectivity for the Delta-Opioid Receptor over the Mu-Opioid Receptor In Vitro and In Vivo.

Positive allosteric modulators (PAMs) of the delta-opioid receptor (DOR) enhance endogenous opioid signaling while avoiding the convulsant liability of orthosteric agonists. However, the prototypical DOR-PAM, BMS-986187, also potentiates mu-opioid receptor (MOR) signaling, raising concerns regarding respiratory depression and abuse liability. Here, we report a structure-activity study of the benzyloxy moiety of BMS-986187 to improve selectivity for DOR over MOR, while retaining DOR-PAM potency. Fifty-two new analogues and 12 previously reported ones featuring mono- and disubstitution of the benzyl ring and phenyl-heterocycle replacements were synthesized and evaluated in β-arrestin2 recruitment assays. Ortho-substituted derivatives consistently enhanced DOR-PAM potency, although often increased MOR-PAM activity. One pyridyl derivative (compound 35) retained high DOR-PAM potency and efficacy (EC50 = 0.1 μM, Emax = 91%) with no detectable MOR activity. In mice, compound 35 enhanced DOR-mediated reversal of nitroglycerin-induced hyperalgesia, an effect absent in DOR-knockout mice, without enhancing MOR-mediated antinociception, demonstrating in vivo selectivity.

Receptors, Opioid, delta↗

PubMed2004

Oleic acid derived metabolites in mouse neuroblastoma N18TG2 cells.

Oleamide is an endogenous sleep-inducing lipid that has been isolated from the cerebrospinal fluid of sleep-deprived mammals. Oleamide is the best-understood member of the primary fatty acid amide family. One key unanswered question regarding oleamide and all other primary acid amides is the pathway by which these molecules are produced. One proposed pathway involves oleoyl-CoA and N-oleoylglycine as intermediates: oleic acid --> oleoyl-CoA --> N-oleoylglycine --> oleamide. The first and third reactions are known reactions, catalyzed by acyl-CoA synthetase and peptidylglycine alpha-amidating monooxygenase (PAM). Oleoyl-CoA formation from oleic acid has been demonstrated in vitro and in vivo while, to date, N-oleoylglycine cleavage to oleamide has been established only in vitro. PAM catalyzes the final step in alpha-amidated peptide biosynthesis, and its proposed role in primary fatty acid amide biosynthesis has been controversial. Mouse neuroblastoma N(18)TG(2) cells are an excellent model system for the study of oleamide biosynthesis because these cells convert [(14)C]-oleic acid to [(14)C]-oleamide and express PAM in a regulated fashion. We report herein that growth of the N(18)TG(2) cells in the presence of [(14)C]-oleic acid under conditions known to stimulate PAM expression generates an increase in [(14)C]-oleamide or in the presence of a PAM inhibitor generates [(14)C]-N-oleoylglycine. This represents the first identification of N-oleoylglycine from a biological source. In addition, N(18)TG(2) cell growth in the presence of N-oleoylglycine yields oleamide. These results strongly indicate that N-oleoylglycine is an intermediate in oleamide biosynthesis and provide further evidence that PAM does have a role in primary fatty acid amide production in vivo.

Animals↗

PubMed1995

Clinical comparison of three techniques for evaluating visual function behind cataract.

The aim of the study was to compare the ability of displacement threshold hyperacuity to identify reduced retinal/neural function in cataract patients with that of the potential acuity meter (PAM) and laser interferometer. Fifty-two patients (mean age 72.0 +/- 10.8 years) admitted for extracapsular cataract extraction were randomly selected for inclusion in the study. Patients underwent routine refraction and logMAR acuity measurement on the eve of cataract surgery. Following pupillary dilation and in random order, the oscillatory displacement threshold (ODT; defined as the smallest detectable displacement of an object) was determined, and predictions of the post-operative acuity were obtained using the PAM and Rodenstock Retinometer (RR). Patients were re-examined approximately 7 weeks post-operatively when logMAR acuities and ODTs were remeasured. On the basis of the results of an independent fundus examination, patients were assigned to either a normal or a pathology group. Increasing cataract density adversely affected the predictions provided by the PAM (p = 0.0001) and ODT (p = 0.0001) techniques, but not the RR (p = 0.137). One-factor ANOVA revealed that pre-operative ODT (p = 0.0001), PAM (p = 0.0001) and RR (p = 0.0004) measures successfully distinguished patients with retinal/neural pathology from normals. Pre-operative cut-off levels to distinguish normal from pathology cases were retrospectively determined for each technique. The cut-off values for the PAM and ODT techniques yielded higher sensitivity and specificity values than was the case for the RR. The results suggest that the predictive abilities of the PAM and ODT techniques are similar, and superior to that of the RR. Further work involving larger numbers of patients with posterior segment pathology is necessary to reveal which technique provides the best means of assessing retinal/neural function in the presence of ocular media opacities.

Aged↗

PubMed1997

Importance of aspartate-70 in organophosphate inhibition, oxime re-activation and aging of human butyrylcholinesterase.

Asp-70 is the defining amino acid in the peripheral anionic site of human butyrylcholinesterase (BuChE), whereas acetylcholinesterase has several additional amino acids, the most important one being Trp-277 (Trp-279 in Torpedo AChE). We studied mutants D70G, D70K and A277W to evaluate the role of Asp-70 and Trp-277 in reactions with organophosphates. We found that Asp-70 was important for binding positively charged echothiophate, but not neutral paraoxon and iso-OMPA. Asp-70 was also important for binding of positively charged pralidoxime (2-PAM) and for activation of re-activation by excess 2-PAM. Excess 2-PAM had an effect similar to substrate activation, suggesting the binding of 2 mol of 2-PAM to wild-type but not to the D70G mutant. A surprising result was that Asp-70 was important for irreversible aging, the D70G mutant having a 3- and 8-fold lower rate of aging for paraoxon-inhibited and di-isopropyl fluorophosphate-inhibited BuChE. Mutants of Asp-70 had the same rate constants for phosphorylation and re-activation by 2-PAM as wild-type. The A277W mutant behaved like wild-type in all assays. Our results predict that people with the atypical (D70G) variant of BuChE will be more sensitive to the toxic effects of echothiophate, but will be equally sensitive to paraoxon and di-isopropyl fluorophosphate. People with the D70G mutation will be resistant to re-activation of their inhibited BuChE by 2-PAM, but this will be offset by the lower rate of irreversible aging of inhibited BuChE, allowing some regeneration by spontaneous hydrolysis.

Acetylcholinesterase↗

PubMed1997

Suppression of substance P biosynthesis in sensory neurons of dorsal root ganglion by prodrug esters of potent peptidylglycine alpha-amidating monooxygenase inhibitors.

Substance P as well as many other neuropeptides are synthesized as glycine-extended precursors and converted to the biologically active C-terminal amides by posttranslational modification. The final step of posttranslational processing is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM). In a previous study, N-substituted homocysteine analogs were found to be potent inhibitors of PAM partially purified from conditioned medium of cultured rat medullary thyroid carcinoma CA-77 cells. These compounds, however, were only modest inhibitors of substance P production in cultured dorsal root ganglion cells, possibly because of poor cell penetration. Several ester derivatives of hydrocinnamoyl-phenylalanyl-homocysteine, one of the most potent PAM inhibitors, were prepared to increase the intracellular accessibility of these compounds. Hydrocinnamoyl-phenylalanyl-(S-benzoyl-homocysteine) benzyl ester was identified as the most potent compound, inhibiting substance P biosynthesis in dorsal root ganglion cells with an IC50 of 2 microM. Inhibition of PAM resulted in a concomitant increase in the glycine-extended substance p (substance P-Gly) precursor peptide. In the presence of 3 microM benzyl ester derivative, the intracellular substance P-Gly level was 2.4-fold higher while the substance P level was 2.1-fold lower than the corresponding peptides in control cells. These results suggest that PAM inhibition represents an effective method for suppression of substance P biosynthesis and, therefore, may have therapeutic utility in conditions associated with elevated substance P levels. Furthermore, PAM inhibition may also prove useful in decreasing other amidated peptides.

Animals↗

PubMed2000

Targeting of membrane proteins to the regulated secretory pathway in anterior pituitary endocrine cells.

Unlike the neuroendocrine cell lines widely used to study trafficking of soluble and membrane proteins to secretory granules, the endocrine cells of the anterior pituitary are highly specialized for the production of mature secretory granules. Therefore, we investigated the trafficking of three membrane proteins in primary anterior pituitary endocrine cells. Peptidylglycine alpha-amidating monooxygenase (PAM), an integral membrane protein essential to the production of many bioactive peptides, is cleaved and enters the regulated secretory pathway even when expressed at levels 40-fold higher than endogenous levels. Myc-TMD/CD, a membrane protein lacking the lumenal, catalytic domains of PAM, is still stored in granules. Secretory granules are not the default pathway for all membrane proteins, because Tac accumulates on the surface of pituitary endocrine cells. Overexpression of PAM is accompanied by a diminution in its endoproteolytic cleavage and in its BaCl(2)-stimulated release from mature granules. Because internalized PAM/PAM-antibody complexes are returned to secretory granules, the endocytic machinery of the pituitary endocrine cells is not saturated. As in corticotrope tumor cells, expression of PAM or Myc-TMD/CD alters the organization of the actin cytoskeleton. PAM-mediated alterations in the cytoskeleton may limit maturation of PAM and storage in mature granules.

Actins↗

PubMed2006

The maintenance of high affinity plasminogen binding by group A streptococcal plasminogen-binding M-like protein is mediated by arginine and histidine residues within the a1 and a2 repeat domains.

Subversion of the plasminogen activation system is implicated in the virulence of group A streptococci (GAS). GAS displays receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M-like protein (PAM). The plasminogen binding domain of PAM is highly variable, and this variation has been linked to host selective immune pressure. Site-directed mutagenesis of full-length PAM protein from an invasive GAS isolate was undertaken to assess the contribution of residues in the a1 and a2 repeat domains to plasminogen binding function. Mutagenesis to alanine of key plasminogen binding lysine residues in the a1 and a2 repeats (Lys98 and Lys111) did not abrogate plasminogen binding by PAM nor did additional mutagenesis of Arg101 and His102 and Glu104, which have previously been implicated in plasminogen binding. Plasminogen binding was only abolished with the additional mutagenesis of Arg114 and His115 to alanine. Furthermore, mutagenesis of both arginine (Arg101 and Arg114) and histidine (His102 and His115) residues abolished interaction with plasminogen despite the presence of Lys98 and Lys111 in the binding repeats. This study shows for the first time that residues Arg101, Arg114, His102, and His115 in both the a1 and a2 repeat domains of PAM can mediate high affinity plasminogen binding. These data suggest that highly conserved arginine and histidine residues may compensate for variation elsewhere in the a1 and a2 plasminogen binding repeats, and may explain the maintenance of high affinity plasminogen binding by naturally occurring variants of PAM.

Amino Acid Sequence↗

PubMed1994

Chemiluminescence properties of porcine pulmonary alveolar macrophages and polymorphonuclear cells.

A luminol-enhanced chemiluminescence (CL) technique was developed for porcine pulmonary alveolar macrophages (PAM) and polymorphonuclear cells (PMN). PAM were obtained from lung washings of 3 week old gnotobiotic pigs. PMN were obtained from peripheral blood by separation on a discontinuous Percoll gradient. Optimum CL signals were obtained with 10(5) PAM/tube and 5 x 10(4) PMN/tube. Stimulation indexes (SI) for PAM were approximately 10 for phorbol myristate acetate (PMA), 8 for opsonized Actinobacillus pleuropneumoniae and 3 for opsonized zymosan. SI for PMN varied from 100 to 180 for complement opsonized zymosan, from 50 to 100 for opsonized A. pleuropneumoniae and from 10 to 20 for PMA. Formyl-methionyl-phenylalanine and calcium ionophore A23187 did not stimulate the oxidative activity of PAM or PMN. PAM that had been frozen and stored in liquid nitrogen reacted as freshly obtained PAM in the CL assay; however, PMN that had been frozen lost a great deal of their ability to produce oxygen radicals after thawing. The CL technique offers new perspectives for the study of immune mechanisms in swine.

Animals↗

PubMedDate not supplied

Effect of in vivo ozone exposure on in vitro pulmonary alveolar macrophage mobility.

The effect of in vivo O3 exposure on the mobility of pulmonary alveolar macrophages (PAM) in vitro was investigated. Eight randomly selected rats were exposed for 4 h. Four rats were exposed to a clean air (sham) atmosphere, and four to an atmosphere containing 1ppm O3. PAM were obtained by lung lavage and placed on gold-colloid coated coverslips. The area cleared of gold particles by migrating PAM after 24, 48, and 72 h was used as an indicator of cell mobility. The number of PAM recoverable by lavage was similar for both groups (2 x 10(5)), but the percentage of macrophages that made tracks was significantly smaller with 95% certainty in the O3 group. For sham-exposed and O3-exposed groups, the area cleared by PAM increased as the length of incubation increased, with the area cleared by the sham-exposed group being about 50% greater during each time period. When the two groups were compared statistically at each time point, the probability that they differed was, in each case, greater than 95%. It was concluded that the in vitro migrational potential of PAM was most likely decreased by in vivo exposure to O3.

Animals↗