White Carneau Pigeons Research Articles

Age-related reductions in whole brain mass and telencephalon volume in very old white Carneau pigeons (Columba livia)

While studies have identified age-related cognitive impairment in pigeons (Columba livia), no study has detected the brain atrophy which typically accompanies cognitive impairment in older mammals. Instead, Coppola and Bingman (Aging is associated with larger brain mass and volume in homing pigeons (Columba livia), Neurosci. Letters 698 (2019) 39–43) reported increased whole brain mass and telencephalon volume in older, compared to younger, homing pigeons. One reason for this unexpected finding might be that the older pigeons studied were not old enough to display age-related brain atrophy. Therefore, the current study repeated Coppola and Bingman, but with a sample of older white Carneau pigeons that were on average 5.34 years older. Brains from young and old homing pigeons were weighed and orthogonal measurements of the telencephalon, cerebellum, and optic tectum were obtained. Despite having a heavier body mass than younger pigeons, older pigeons had a significant reduction in whole brain mass and telencephalon volume, but not cerebellum or optic tectum volume. This study is therefore the first to find that pigeons experience age-related brain atrophy.

Cutaneous leiomyosarcoma with visceral metastases in a White Carneau pigeon and literature review.

Cutaneous leiomyosarcomas are malignant mesenchymal tumors of smooth muscle origin and are reported occasionally in avian species. A 14-y-old male laboratory White Carneau pigeon (Columba livia) was presented for surgical excision of a cervical soft tissue mass. Ultrasonography with color flow Doppler imaging revealed multiple cavitations of mixed echogenicity within the mass and vascularization. Histologically, the dermis and subcutis were expanded by a densely cellular multinodular mass comprised of fusiform cells forming haphazardly arranged broad streams and short interwoven bundles, often surrounding blood vessels and variably sized cavitations. Neoplastic cells were strongly immunopositive for desmin and α-smooth muscle actin, and negative for pancytokeratin, S100, and von Willebrand factor. Based on histopathology and IHC findings, the cutaneous mass was diagnosed as leiomyosarcoma (LMS). The pigeon died 312 d post-operatively. Postmortem examination revealed masses infiltrating the left and right pulmonary airways and one hepatic nodule, but no regrowth at the surgical site. Histologic and IHC evaluation of the pulmonary and hepatic masses were consistent with LMS, representing metastatic foci from the primary cutaneous LMS. Our case highlights the malignant behavior and histomorphologic features of cutaneous LMS in an avian species.

EFFECTS OF PERCENT REINFORCEMENT ON PIGEON'S ACCURACY IN MIDSESSION REVERSAL TASKS [University of Kentucky

This experiment tests the effects of a reducing the value of one stimulus compared to another. We hypothesize that in a midsession reversal task, accuracy would improve by devaluing choice of S2 relative to S1. A midsession reversal task requires a simultaneous discrimination between 2 stimuli (S1, S2), during which, halfway through the session the reinforcing stimulus is reversed. A current theory, win-stay/lose-shift, is a strategy for optimal choices in this task. In this strategy, an animal would continue to repeat choice of a correct stimulus, but once the stimulus becomes incorrect, the animal should switch to the other stimulus. In this experiment, ten unsexed White Carneau pigeons were used as subjects. The experiment took place in an operant test chamber. Inside, three horizontally aligned circular response keys are attached to a response panel. The keys are lit by mounted projectors showing red and green hues. Reinforcement consisted of 1.5 seconds of access to mixed-grain from a feeder. In the experimental group, all correct responses to S1 were reinforced but only a random 20% of the correct responses to S2 were reinforced. Our findings suggest that paradoxically, the reduction in the probability of reinforcement for correct S2 responses from 100% to 20% had a net positive effect on correct responses. There was a significant reduction in errors prior to the feedback from the reversal as well as no increase in errors following the feedback from the reversal. Analysis of the trials on either side of the reversal made it clear that there was a net benefit in percentage correct due to the decrease in the probability of reinforcement associated with correct responses to S2. This study suggests the negative impacts of too much reinforcement on subjects performance in a task.

GENERALIZED IDENTITY MATCHING IN THE PIGEON: ROLE OF EXTENDED OBSERVING- AND CHOICE-RESPONSE REQUIREMENTS

Four experimentally naive White Carneau pigeons matched three hues to each other in a variant of an identity matching-to-sample procedure with a fixed-ratio 20 on samples and a response-initiated fixed-interval 8 s on comparisons. The extent to which the pigeons were matching on the basis of identity was assessed by presenting, in extinction, test trials comprising novel stimuli serving as the sample and comparison stimuli. When the test trials were comprised only of novel stimuli, three out of the four pigeons demonstrated substantially above-chance levels of accuracy. These data suggest that the extended observing- and choice-response requirements facilitate the development of generalized identity matching performance.

Atherosclerosis-susceptible and atherosclerosis-resistant pigeon aortic cells express different genes in vivo

Spontaneous atherosclerosis in the White Carneau (WC-As) pigeon is inherited as a single gene disorder, and its progression closely mirrors the human disease. Representational difference analysis and microarray were used to identify genes that were differentially expressed between the susceptible WC-As and resistant Show Racer (SR-Ar) aortic tissue. The RNA extracted from 1-d-old squab aortas was used to make cDNA for each experiment. Fifty-six unique genes were found using representational difference analysis, with 25 exclusively expressed in the WC-As, 15 exclusive to the SR-Ar, and 16 nonexclusive genes having copy number variation between breeds. Caveolin and β-actin were expressed in the WC-As, whereas the proteasome maturation protein and the transcription complex CCR4-NOT were exclusive to the SR-Ar. Microarray analysis revealed 48 genes with differential expression. Vascular endothelial growth factor and p53 binding protein were among the 17 genes upregulated in the WC-As. Thirty-one genes were upregulated in the SR-Ar including the transforming growth factor-β signaling factor SMAD2 and heat shock protein 90. Genes representing several biochemical pathways were distinctly different between breeds. The most striking divergences were in cytoskeletal remodeling, proteasome activity, cellular respiration, and immune response. Actin cytoskeletal remodeling appears to be one of the first differences between susceptible and resistant breeds, lending support to the smooth muscle cell phenotypic reversion hypothesis of human atherogenesis.

Differentially expressed genes in aortic smooth muscle cells from atherosclerosis-susceptible and atherosclerosis-resistant pigeons

Susceptibility to spontaneous atherosclerosis in the White Carneau (WC-As) pigeon shows autosomal recessive inheritance. Aortic smooth muscle cells (SMC) cultured from susceptible WC-As and resistant Show Racer (SR-Ar) pigeons exhibit developmental and degenerative features corresponding to the respective SMC at atherosclerosis-prone sites in vivo. We used representational difference analysis to identify differentially expressed genes between WC-As and SR-Ar aortic SMC. Total RNA was extracted from cultured primary SMC of each breed, converted to double-stranded cDNA, followed by direct comparison in reciprocal representational difference analysis experiments. Difference products were cloned, sequenced, and identified by BLAST against the chicken genome. Six putative biochemical pathways were distinctly different between breeds with genes involved in energy metabolism and contractility exhibiting the most striking disparity. Genes associated with glycolysis and a synthetic SMC phenotype were expressed in WC-As cells. In contrast, SR-Ar cells expressed genes indicative of oxidative phosphorylation and a contractile SMC phenotype. In WC-As cells, the alternatives of insufficient ATP production limiting contractile function or the lack of functional contractile elements downregulating ATP synthesis cannot be distinguished due to the compressed in vitro versus in vivo developmental time frame. However, the genetic potential for effectively coupling energy production to muscle contraction present in the resistant SR-Ar was lacking in the susceptible WC-As.

INFLUENCES ON COCAINE TOLERANCE ASSESSED UNDER A MULTIPLE CONJUNCTIVE SCHEDULE OF REINFORCEMENT

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key-pecking responses of White Carneau pigeons maintained under a three-component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose-effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response-rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule-parameter-specific tolerance. Tolerance to cocaine was generally independent of FI-parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.

Effect of testosterone and oxandrolone on thrombocyte aggregation and synthesis of prostaglandins in thrombocytes and aorta of atherosclerosis-susceptible pigeons.

Effect of intramuscular administration (10 mg/kg/week) of testosterone and oxandrolone on a) thrombocyte aggregation and b) synthesis of prostaglandins from [14C]-arachidonic acid in thrombocytes and aorta of atherosclerosis-susceptible White Carneau pigeon was examined. Neither testosterone nor oxandrolone influenced collagen, ADP and arachidonic acid induced aggregation or the synthesis of prostaglandins in thrombocytes. However, both testosterone and oxandrolone stimulated (p less than 0.05) the synthesis of 6-keto-PGF1 alpha (stable product of prostacyclin) und PGE2 in aorta.

Comparison Between Co2Laser and 4.0 MHz Radiosurgery for Incising Skin in White Carneau Pigeons (Columba Livia)

To objectively evaluate the collateral damage associated with radiosurgical and carbon dioxide (CO2) laser devices, a comparative surgical and histologic study was undertaken in white Carneau pigeons (Columba livia). Ten pigeons were anesthetized, and a series of 3 skin incisions were made in the pectoral region by using a 4.0-MHz radiosurgical unit, a CO2 laser, and a scalpel blade (control). A total of 90 skin incisions were microscopically evaluated, and their associated mechanical- and thermal-induced tissue lesions were measured in micrometers. Scalpel incisions invariably resulted in hemorrhage, whereas all laser and radiosurgical skin incisions were essentially bloodless. Scalpel blade incisions were least traumatic (mean [SD] 18 +/- 15 microm) followed by incisions created with radiosurgery (mean [SD] 94 +/- 60 microm) and CO2 laser (mean [SD] 150 +/- 64 microm). Radiosurgery was significantly less traumatic than CO2 laser (P = .003). Radiosurgery appears to offer significant benefits over CO2 laser for avian surgery.

Evaluation of Coelioscopic Splenic Biopsy and Cloacoscopic Bursa of Fabricius Biopsy Techniques in Pigeons (Columba livia)

Techniques for endoscopic biopsy of the spleen and bursa of Fabricius were evaluated in 71 juvenile and adult white Carneau pigeons (Columba livia). Splenic biopsy was performed under isoflurane anesthesia by a left lateral approach to the coelom from behind the last rib. From within the left abdominal air sac, the spleen was located just caudal to the isthmus of the proventriculus and ventriculus and ventral to the gonad in 86% of pigeons examined. In the remaining 14%, extensive reproductive activity within mature female pigeons prevented visualization of the spleen. Splenic biopsy samples were successfully obtained from all birds in which the spleen could be found, and all were determined to be of good to excellent histologic quality. Endoscopic biopsy of the bursa of Fabricius was accomplished by cloacoscopy and saline irrigation with the pigeons in dorsal recumbency. The bursa of Fabricius was located and a biopsy was done in 28 (39%) of 71 pigeons. Initial histopathologic evaluation indicated that only 30% of the biopsy samples possessed lymphoid tissue of diagnostic quality. Splenic biopsy via coelioscopy appeared safe and rewarding in pigeons. Cloacoscopy provided an excellent view of the cloaca and appeared to be well tolerated; however, biopsy of the bursa of Fabricius is not recommended because of poor diagnostic value of the specimens and the risk of cloacal perforation.

Artery regional properties and atherosclerosis susceptibility

White carneau (WC) pigeons develop spontaneous atherosclerosis in contrast to atherosclerosis-resistant show racer (SR) pigeons. In this study, cellular and extracellular components and smooth muscle cell (SMC) proliferation rates of specific aortic sites were assessed in both breeds of pigeons prior to lesion development. The atherosclerosis-susceptible site of the WC aorta was characterized by larger lumen diameter without accompanying increase in wall thickness, as well as by SMC hypocellularity, increased proteoglycan content and higher elastin content. For both breeds, cells derived from the lesion site had lower proliferation rates compared to proximal aortic control sites. WC cells had greater proliferation rates than SR cells (109% greater at the atherosclerosis-prone site and 133% greater at the control site). Fibroblast growth factor (FGF) increased the proliferation of WC lesion site cells compared to SR cells (79% vs. 35%); whereas, transforming growth factor β (TGFβ) reduced growth in SR but not in WC cells. Differences in hemodynamic properties, in cell-matrix, elastin, proteoglycan and proliferation rates of cells and responses to FGF and TGFβ in cells of the atherosclerosis-prone area have been identified as potential contributors to the enhanced atherosclerosis potential of this site in WC pigeons.

STAT4 and the proliferation of artery smooth muscle cells in atherosclerosis

Artery smooth muscle cell proliferation is of key importance in the development of atherosclerosis and restenosis following PTCA. In order to understand gene regulation involved in these processes, vascular smooth muscle cells (VSMCs) from atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons were used to identify transcription factors involved in the enhanced proliferation of WC VSMCs. With protein/DNA array, signal transducer and activator of transcription 4 (STAT4) was found to have over a 10-fold increase in expression in WC compared to SR VSMCs. The difference was confirmed with electrophoretic-mobility shift assay (EMSA) and Western blot. Cells cultured under low serum had 5-fold higher levels of STAT4 in WC compared to SR. By Western analysis, aortic tissue from newly hatched WC pigeons had 1.7–2.0 times greater STAT4 expression than in SR pigeons. A pathway whereby enhanced STAT4 may be associated with enhanced proliferation was identified following IL-12 stimulation of WC VSMCs where 3-fold increases in proliferation and 2-fold higher expression of STAT4 were measured. The findings suggest STAT4 may play a role in VSMC proliferation and describe a unique pigeon model system in which to study STAT4 as a gene target for atherosclerosis therapy.

Reduced syndecan-4 expression in arterial smooth muscle cells with enhanced proliferation

Syndecans, a family of cell surface heparan sulfate (HS) containing proteoglycans (PGs), are known regulators of many biological processes including inhibition of smooth muscle cell (SMC) proliferation. Cultured arterial SMCs from atherosclerosis-susceptible White Carneau (WC) pigeons have increased proliferation rates and significant reductions in total cell-surface HS relative to atherosclerosis-resistant Show Racer (SR) SMC. Using a specific syndecan-4 cDNA, 1.5- to 2.0-fold reductions in gene expression were observed in WC SMC compared to SR SMC. Immunolocalization studies demonstrated reduced cell surface syndecan-4 protein in WC cells. Gene induction demonstrated that the reduction in syndecan-4 expression in WC cells was not due to reduced mRNA stability. Studies using cycloheximide to superinduce gene expression indicated transcriptional suppression of syndecan-4 in WC cells. The results suggest that reduced cell surface HS PG in WC arterial SMC can be explained, in part, by reductions in syndecan-4 gene expression. Differential transcriptional regulation of syndecan-4 in WC and SR cells provides a system to explore regulation of the syndecan-4 gene as well as the potential mechanisms by which syndecan-4 can exert a specific antiproliferative effect.

Pulmonary Leiomyosarcoma in a White Carneau Pigeon (Columba livia)

A unique case of primary pulmonary leiomyosarcoma was diagnosed postmortem in an adult white Carneau pigeon (Columba livia) that had presented with respiratory distress, lethargy, and anorexia nonresponsive to antibiotic treatment. Histologically, the pulmonary mass was composed of multiple interlacing bands of malignant spindle cells. Prominent eosinophilic staining of these cells with Masson trichrome stain and immunohistochemical staining that was positive for actin and desmin confirms smooth muscle origin. This is the first report of a primary pulmonary leiomyosarcoma in a pigeon.

Three-choice discrimination in pigeons is based on relative efficacy differences among opioids.

Drug discrimination assays can provide important information on receptor selectivity and relative efficacy to guide the classification and characterization of opioid agonists. A three-choice discrimination was established among high efficacy opioid agonist morphine, low efficacy opioid agonist nalbuphine, and saline to examine the conditions under which differences in relative efficacy might serve as a basis for stimulus control. Seven White Carneau pigeons were trained to discriminate among 5.6 mg/kg nalbuphine, 3.2 mg/kg morphine, and saline under fixed ratio 30 (FR30) schedules of food reinforcement. Substitution and antagonism experiments were then conducted with mu, kappa, and delta opioids and naltrexone, respectively and the percent responding appropriate to the training stimuli was determined. Low, intermediate, and high doses of morphine produced > or = 80% saline-, > or = 60% nalbuphine-, and > or = 96% morphine-appropriate responding, respectively. Low and high doses of nalbuphine produced > or = 80% saline- and nalbuphine-appropriate responding, respectively. In substitution tests, low doses of fentanyl and etorphine produced partial nalbuphine-appropriate responding (20-60%) and high doses produced > or = 60-80% morphine-appropriate responding. Intermediate doses of buprenorphine and dezocine produced > or = 60-80% nalbuphine-appropriate responding and high doses produced > or = 80% morphine-appropriate responding. The lower efficacy agonists butorphanol, nalorphine, and levallorphan produced > or = 40-80% nalbuphine-appropriate responding. The kappa agonists spiradoline and U50,488 produced approximately > or = 50% nalbuphine-appropriate responding whereas d-amphetamine, saline, and delta agonists BW373U86 and SNC 80 produced > or = 80% saline-appropriate responding. Naltrexone produced > or = 80% saline-appropriate responding and reversed the stimulus effects of morphine and nalbuphine. The discrimination between morphine and nalbuphine in pigeons is predominantly based on the relative efficacy differences between morphine, a higher-efficacy mu agonist and nalbuphine, a lower-efficacy mu agonist.

Distribution of Disease around the Aortocoeliac Branch of White Carneau Pigeons at Different Ages

The distribution of atherosclerotic lesions in the human aorta changes with age. Lipid deposition tends to occur downstream of branch sites in immature vessels but upstream of them at later ages. Comparable age-related distributions of spontaneous and induced lesions have been demonstrated in rabbit aortas. Spontaneous disease is known to develop upstream of the aortocoeliac branch in mature White Carneau pigeons. Using a frequency mapping technique, we investigated whether the same pattern or a downstream one occurs in immature pigeons. Lesions in hatchlings occurred upstream of the branch, to the left of the midline. By 5 months, these lesions had expanded, and a second upstream area, to the right of the midline, was also affected. At later ages, disease frequencies increased in both of these regions but not elsewhere. Thus, contrary to findings in rabbit and human aortas, there was no evidence for a switch from a downstream to an upstream distribution with age. The two rabbit distributions have been attributed to the similar age-related patterns seen in the permeability of the arterial wall; the mature but not the immature pattern of permeability is NO-dependent. The absence of the juvenile disease pattern in pigeons suggests that they might show the NO-dependent pattern of permeability at all ages.

Variable-Interval Schedule Control Following Response Acquisition with Delayed Reinforcement

Four experimentally naive White Carneau pigeons acquired a key-peck response without specific response shaping or other training when such responding was reinforced according to a tandem variable-interval t-s differential-reinforcement-of-otherbehavior 30-s schedule. This schedule defined an unsignaled, resetting delay-of-reinforcement procedure. When subsequently exposed to a variable-interval schedule of immediate reinforcement, response rates increased rapidly, usually within a single 90-min session. The response rates of the pigeons under this latter condition were comparable to those of other pigeons with a history of responding only on variable-interval schedules of reinforcement, with reinforcement rates and distributions yoked to the delay of reinforcement condition. Two other pigeons exposed to a schedule of response-independent food delivery, yoked in terms of food delivery rate to the tandem schedule, did not peck consistently and eventually stopped responding. The results suggest that the persistence of low-rate responding often reported in studies of behavioral history effects is not universal. Rather, it is a product of both experimenter-arranged and naturally occurring specific past and current contingencies.

Impaired function of lecithin:cholesterol acyltransferase in atherosclerosis-susceptible White Carneau pigeons: possible effects on metabolism of oxidized phospholipids

Although White Carneau (WC) pigeons are known to be more susceptible to atherosclerosis than Show Racer (SR) pigeons, the reasons for this difference are not fully understood. While no major differences are known in the lipoprotein composition, a difference in the cholesteryl ester (CE) composition was reported. However, there is little information on the activity or specificity of lecithin:cholesterol acyltransferase (LCAT), the major source of plasma CE. In order to determine whether the esterification of cholesterol or other functions of LCAT are compromised in WC pigeons, we studied the various reactions catalyzed by LCAT in the two groups. The cholesterol esterification was found to be significantly lower in WC pigeons, whether assayed with exogenous or endogenous substrates. Furthermore, lyso phosphatidylcholine (PC) esterification and oxidized PC hydrolysis, two other reactions carried out by LCAT, were also lower in WC. We found evidence for the presence of an active lysophospholipase in pigeon plasma, and this activity was also lower in WC compared to SR. A significant increase in the FC/PC ratio, another reported atherogenic risk factor, was found in WC plasma. Because of the absence of other hydrolytic enzymes in pigeon plasma, LCAT may play an important role in the metabolism of oxidized PC generated during lipoprotein oxidation, and therefore a decrease in its activity in White Carneau pigeons may contribute to increased risk of atherosclerosis.—Liu, M., R. W. St. Clair, and P. V. Subbaiah. Impaired function of lecithin:cholesterol acyltransferase in atherosclerosis-susceptible White Carneau pigeons: possible effects on metabolism of oxidized phospholipids.

Cellular dynamics in early atherosclerotic lesion progression in white carneau pigeons. Spatial and temporal analysis of monocyte and smooth muscle invasion of the intima.

The early stages of atherosclerosis are characterized by macrophage invasion of the intimal space and proliferation of smooth muscle cells (SMCs). In this study, we characterize the timing and location of each of these processes. Dividing cells of the developing lesions were labeled with [3H]thymidine at different times during lesion progression. Comparable stages of lesion development were analyzed, with the only variable being the length of time between labeling and necropsy. In this way, the mechanism by which lesion composition changes could be inferred from changes in the distribution of label over time. When cells were labeled just before necropsy, serial sections showed monocyte influx predominantly occurring at lesion edges and resulting in a labeling index of 27%. Near the lesion edge, medial SMCs were not stimulated to proliferate. In contrast, in more central areas of the lesion, monocyte influx and intimal SMC proliferation were minimal. Medial SMC proliferation in central regions, however, was high, with a labeling index of 20% in the upper media. Over time, proliferating medial SMCs migrated into the intimal lesion but did not migrate laterally to any great extent. This migration pattern maintained precise subdomains during lesion development, with each domain representing a different stage of lesion development. The edge of lesions thus represents very early events, central regions indicate later events, and intermediate regions provide information about stages between these extremes.

Characterization of α2-macroglobulin receptor low density lipoprotein receptor-related protein ( α2MR/LRP) in White Carneau pigeon peritoneal macrophages: its role in lipoprotein metabolism

White Carneau pigeons develop atherosclerosis naturally, and at an accelerated rate with cholesterol feeding. Macrophages play a central role in the pathogenesis of atherosclerosis in pigeons, as they do in man. The purpose of this study was to determine whether pigeon macrophages express the α 2-macroglobulin receptor/low density lipoprotein receptor-related protein ( α 2 MR/LRP) and whether this receptor would recognize β-VLDL, the major cholesterol-transporting lipoprotein in cholesterol-fed pigeons. The binding of 125I-methylamine-treated α 2M ( 125I- α 2M +) at 4°C was saturable (>10 nM), specific, Ca 2+ dependent, was competed for by the receptor-associated protein (RAP), and had a K d of binding of 1–5.6 nM, similar to mouse peritoneal macrophages studied simultaneously. At 37°C the bound 125I- α 2M + was rapidly internalized and degraded in lysosomes. The binding of α 2M + was not down-regulated with cholesterol loading, as is the LDL receptor on pigeon macrophages. At 4°C there was no competition for binding of 125I- α 2M + by either pigeon or rabbit β-VLDL, nor was binding of 125I-pigeon or rabbit β-VLDL competed for by α 2M +. Stimulation of cholesterol esterification by rabbit or pigeon β-VLDL was unaffected by RAP, lactoferrin, or α 2M +. Metabolism of 125I-pigeon or rabbit β-VLDL was not competed by RAP, lactoferrin, or α 2M + even in the presence of lipoprotein lipase. Pigeon macrophages, and a 500 kDa membrane protein isolated from them, were recognized by several antihuman α 2MR/LRP monoclonal antibodies. The 500 kDa membrane protein also bound 45Ca. These data suggest considerable sequence homology with the human α 2MR/LRP. This is the first study to characterize a functional α 2MR/LRP on peritoneal macrophages from an avian species. There was no evidence, however, that the α 2MR/LRP mediates uptake of β-VLDL by pigeon macrophages.