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Biomedical subjects

M L Entman

Publications and source records attributed to M L Entman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cloning and comparative sequence analysis of the gene encoding canine intercellular adhesion molecule-1 (ICAM-1).

Canine intercellular adhesion molecule-1 (ICAM-1) plays a primary role in the adherence of canine neutrophils to endothelial cells and in the cytotoxicity of canine neutrophils for adult cardiac myocytes. We have cloned the canine ICAM-1 gene and have analyzed the conservation of ICAM-1 amino acid (aa) sequences in man, chimpanzee, mouse, rat and dog. Canine ICAM-1 displays 61% identity with human ICAM-1. Cys residues critical to the immunoglobulin (Ig) fold structure and four sites of N-linked glycosylation are absolutely conserved in ICAM-1 from all species. Residues in the cytoplasmic tail associated with cytoskeletal alpha-actinin binding are highly conserved, supporting the hypothesis that intracellular attachment is indeed important for ICAM-1 function. Residues critical for human ICAM-1 binding to the beta 2-integrin leukocyte-function-associated antigen 1 (LFA-1) are highly conserved between all species, whereas those residues demonstrated to play an important role in interaction of human ICAM-1 with macrophage activation complex 1 (Mac-1) are not highly conserved. Residues critical for ICAM-1 binding to rhinovirus and malaria-infected red blood cells (IRBC) are not highly conserved.

Amino Acid Sequence↗
PubMed1995

Noninvasive measurement of ascending aortic blood velocity in mice.

Mice are useful models in numerous research protocols, but monitoring cardiovascular parameters in small animals is difficult. Therefore we evaluated the use of 20-MHz pulsed Doppler ultrasound to measure ascending aortic blood velocity in intact anesthetized mice. Using a 0.5-mm-diameter 20-MHz transducer applied to the right sternal border, we recorded audio Doppler signals from the ascending aorta of 31 mice [24.4 +/- 1.5 (SD) g body wt]. The signals were played back at speed into a fast Fourier transform analyzer from which we measured heart rate (453 +/- 96 beats/min), ejection time (38 +/- 3%), peak velocity (90 +/- 11 cm/s), mean velocity (23 +/- 4 cm/s), rise time (7.3 +/- 2 ms), stroke distance (29 +/- 7 mm), and acceleration (163 +/- 63 m/s2) from the spectral envelopes. We determined aortic diameter (1.2 +/- 0.2 mm) and Doppler angle (0-20 degrees) in six mice by molding the aortic root and major systemic vessels with casting resin infused at 100 mmHg pressure. For an aortic diameter of 1.2 mm, cardiac output was estimated to be 14.8 ml/min and stroke volume to be 33 microliters. To verify the origin of the signals and to test responsiveness to known stimuli, we measured velocity signals from the aorta and other nearby vessels and varied heart rate and aortic velocity by warming or by infusion of isoproterenol in three open-chest animals. For the noninvasive applications, acoustic coupling was adequate through the moistened fur, and aortic velocity signals were obtained in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Myocardial ischemia and reperfusion: a murine model.

Myocardial ischemia followed by reperfusion promotes a complex series of inflammatory reactions as noted in a variety of large animal studies. With development of genetically altered mice, there is intense interest in developing murine models to study mechanisms operative in cardiovascular disease. We developed a mouse model to study coronary artery occlusion and reperfusion effects and the method required to perform these studies both acutely and chronically. In mice, we applied a left anterior descending coronary artery occlusion either permanently or for 30 or 60 min followed by reperfusion allowing flow through the previously occluded coronary artery bed. Reperfusion was documented visually as well as by using Doppler ultrasound and histopathological techniques. The area at risk (AAR) and infarct size (IS) were assessed by EVans blue dye and triphenyltetrazolium chloride staining with computerized planimetry using an image analysis software program. The infarct as percentage of AAR and IS as percentage of the left ventricle in 13 mice with permanent occlusion was 68.6 +/- 4.4 and 28.0 +/- 2.8%, respectively. Reperfusion after occlusions of 60 and 30 min resulted in a significant decrease in IS as a percentage of the AAR compared with permanent occlusion. Histological examination of the ischemic and reperfused myocardium shows infiltration of leukocytes into the ischemic region as well as contraction bands classically associated with reperfusion. This new model allows assessment of AAR, IS, cardiac function, and pathophysiology in the mouse. With the current technology to develop genetically altered mice for overexpression or targeted mutations of various genes, this model is used to understand the complex pathophysiology of ischemia and reperfusion injury.

Animals↗
PubMed1995

Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo.

Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL-8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.

Amino Acid Sequence↗
PubMed1995

P-selectin- and CD18-mediated recruitment of canine neutrophils under conditions of shear stress.

Neutrophil mobilization at sites of inflammation or thrombosis involves the participation of several adhesion molecules expressed on neutrophils and vascular endothelial cells. Local vascular damage with disruption of the endothelium results in adhesion of platelets to the exposed subendothelium, and these platelets could also participate in neutrophil recruitment. This initial phase of mobilization could be followed by heterotypic aggregation to recruit more leukocytes in the area. The present study first examined the interactions of adherent canine platelets and flowing canine neutrophils using an in vitro system that simulates vascular flow conditions. Results showed that collagen-adherent platelets express the adhesion molecule P-selectin on their surface and can support neutrophil arrest (612 +/- 43 neutrophils/mm2) at shear stresses of approximately 2.5 dynes/cm2. Both transient adhesion (manifested by a rolling-type behavior) and complete arrest were observed. These interactions could be totally inhibited by a monoclonal antibody directed against platelet P-selectin (24 +/- 18 neutrophils/mm2) but not by a monoclonal antibody against neutrophil CD18 (625 +/- 46 neutrophils/mm2). Additionally, under shear mixing conditions (700 RPM), canine blood leukocytes exhibited aggregation (> 80% singlets recruited into aggregates after 5 minutes), and this process does not involve P-selectin but is dependent on the neutrophil integrin CD18. However, stimulation of the blood with platelet-activating factor (5-20 ng/ml) induced a rapid aggregation with a significantly greater number of aggregates when compared with stirring alone (68.3% +/- 3.2% versus 35.2% +/- 6.3% at 1 minute, P < 0.05), and this aggregation was both P-selectin and CD18 dependent. Overall, these two mechanisms of leukocyte recruitment (neutrophil arrest on adherent platelets and aggregation) could act sequentially and in a cooperative manner to bring into close contact platelets and neutrophils at sites of inflammation and thrombosis in pathologic conditions in the dog.

Animals↗
PubMed1994

Free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries.

OBJECTIVES: The purpose of this study was to test the hypothesis that free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured coronary arteries. BACKGROUND: Although free oxygen radicals, such as superoxide anion and hydrogen peroxide, have been shown to alter platelet function in vitro, the potential role of free oxygen radicals has not been fully described in an in vivo model of coronary artery thrombosis. METHODS: Cyclic flow variations were produced in dogs by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery was monitored by a pulsed Doppler flow probe. If cyclic flow variations were observed during postoperative days, dogs intravenously received superoxide dismutase plus catalase. In anesthetized dogs that did not develop an episode of cyclic flow variations, the effect of intracoronary infusion of xanthine plus xanthine oxidase or hydrogen peroxide on arterial blood flow velocity was studied. In platelet studies, the effect of free oxygen radicals and radical scavengers on platelet aggregation was examined. RESULTS: In conscious dogs with cyclic flow variations, superoxide dismutase plus catalase significantly reduced cyclic flow variations (n = 7), whereas saline infusion had no effect (n = 7). The infusion of xanthine plus xanthine oxidase or hydrogen peroxide significantly induced cyclic flow variations in four of six dogs or in five of seven dogs, respectively. In vitro platelet studies showed that xanthine plus xanthine oxidase or hydrogen peroxide significantly enhanced platelet aggregation, and superoxide dismutase or catalase significantly inhibited such aggregation. CONCLUSIONS: Reduction of free radical formation decreases platelet aggregation and may eliminate cyclic flow variations, whereas promotion of free radical generation enhances platelet aggregation and may induce cyclic flow variations. Thus, free oxygen radicals are an important mediator in this model.

Animals↗
PubMed1994

Postreperfusion inflammation: a model for reaction to injury in cardiovascular disease.

In the preceding section various strategies to interdict postreperfusion inflammatory injury of the myocardium were proposed; effectively the strategies were aimed at specific targets such as stimuli which control cell motility, mechanisms of alteration of cell phenotype, and the induction of cell adhesion and proliferation. It is of interest to see how similar these targets would be if one were to attempt a cell biological approach to vascular injury which results in subintimal hyperplasia. In the latter, cells in the media adopt a phenotype which allows cell migration in the direction of a gradient (presumably chemotactic) which directs them to the subintima which is the site of injury. This motility is associated with the expression in these cells of non-muscle myosin and beta actin, both of which are implicated in the motility of leucocytes. Another similarity between acute inflammation and subintimal hyperplasia relates to the role of cellular adhesion as an important determinant of cell motility. As reviewed above, leucocyte motility involves cell adhesion mediated by a class of molecules termed leucocyte integrins (beta 2 integrins) which vary in their alpha subunits and share CD18 as a common beta subunit (CD11a/CD18 = LFA-1, CD11b/CD18 = Mac-1). The activation and inactivation of these integrins is associated with a high and low affinity state, and motility is effected by the cycling of high and low affinity states as well as by cytoskeleton mediated redistribution of adhesion molecules on the leucocyte membrane. In similar fashion, the migration of medial cells and macrophages to the subintima is associated with specific adhesion to extracellular matrix. This adhesion is mediated by similar classes of integrins containing varying alpha subunits and common beta subunits (in this case beta 1 or beta 3) that have been also shown to undergo activation and inactivation cycles yielding high and low affinity states. The similarities between these integrin mediated adhesion events in leucocytes and in the vascular cells is further emphasised by the fact that leucocytes also contain beta 1 integrins; in fact monocytes and T-lymphocytes express a beta 1 integrin (VLA-4) which supports transmigration out of the vascular space via its interaction with VCAM-1 as an alternative to beta 2 integrin-ICAM-1 adhesion. Substantial evidence suggests that integrin mediated adhesion also functions as a transducer of cell secretion of matrix proteins, growth factors, and cytokines from smooth muscle cells, tissue macrophages, transmigrated leucocytes, and endothelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemotactic Factors↗
PubMed1994

Molecular evidence for induction of intracellular adhesion molecule-1 in the viable border zone associated with ischemia-reperfusion injury of the dog heart.

BACKGROUND: Acute inflammation may play a role in injury during reperfusion following myocardial ischemia. Studies in vitro suggest that intracellular adhesion molecule-1 (ICAM-1) mediates neutrophil adherence to cardiac myocytes and neutrophil-mediated injury. We have shown cytokine activity in postischemic cardiac lymph sufficient to maximally express ICAM-1 on myocytes and that ICAM-1 mRNA is found in the previously ischemic myocardium early in reperfusion. METHODS AND RESULTS: In the present study, we used in situ hybridization techniques to detect ICAM-1 mRNA and examine the cells of origin, relation to cell injury, and relation to inflammatory infiltration after 1 hour of ischemia and varying times of reperfusion. By 1 hour of reperfusion, ICAM-1 mRNA was detected in much of the ischemic myocardium, except in areas of contraction band necrosis. At 2 and 3 hours, a clear demarcation of necrotic areas surrounding ischemic areas of viable myocardium with ICAM-1 mRNA staining was present, and ICAM-1 mRNA staining increased with time. Nonischemic areas had no visible ICAM-1 mRNA staining in the first 3 hours. By 24 hours of reperfusion, ICAM-1 mRNA was present in both control and ischemic segments (excluding the necrotic areas) compatible with a generalized circulation of cytokines persistent at 24 hours. In the absence of reperfusion, ICAM-1 mRNA staining was not seen in the first 3 hours and was markedly reduced at 24 hours. The interface of viable and necrotic cells also contained the most extensive inflammatory infiltration. CONCLUSIONS: Evidence is presented that induction of ICAM-1 mRNA has highly specific localization to ischemic but viable myocardium. Induction of ICAM-1 mRNA transcription in early reperfusion may render the viable "border zone" susceptible to neutrophil-induced injury.

Animals↗
PubMed1994

Cardiolipin-protein complexes and initiation of complement activation after coronary artery occlusion.

Specific rabbit anti-cardiolipin (anti-CL) antibodies were used to investigate the hypothesis that cardiolipin, associated with mitochondrial membrane proteins, binds C1 and facilitates activation of the complement cascade following reperfusion of ischemic myocardium. By immunoelectron microscopy, anti-CL localized to subsarcolemmal mitochondria, emerging through breaks in membranes of damaged cardiac myocytes. Anti-CL reacted with > 15 mitochondrial constituents, most of which comigrated with the proteins that bind C1q in transblots of subsarcolemmal mitochondria, fractionated by polyacrylamide gel electrophoresis under reducing conditions in the presence of sodium dodecyl sulfate. A subset of the C1q-binding proteins > 24 to 37 kDa served as stable sites for assembly of C3, C5, and C9. Cardiac lymph, collected during the first hour after reperfusion of ischemic myocardium, contained proteins of diverse size that reacted with both anti-CL and C1q. Cardiac lymph, collected before occlusion and 4 to 5 hours after reperfusion, in comparison, had few if any C1q or anti-CL reactive proteins. Treatment with phospholipase suppressed the C1q-binding activity and anti-CL reactivity of the proteins in reperfusion lymph and those with similar properties in mitochondrial extracts. Our data suggest that during ischemia, mitochondria, extruded through breaks in the sarcolemma, unfold and release membrane fragments in which cardiolipin and protein are intimately associated. By binding C1 and supplying sites for the assembly of later-acting complement components, these fragments provide the means to disseminate the complement-mediated inflammatory response to ischemic injury.

Animals↗
PubMed1994

Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine alveolar macrophages.

Previous studies have demonstrated that alveolar macrophages (AMphis) adherent to plastic release interleukin-8 in response to lipopolysaccharide (LPS). We sought to determine whether LPS could also alter surface adhesion molecule expression and thus modulate additional AMphi adhesive interactions. Canine AMphis obtained by bronchoalveolar lavage of excised lung were adhered onto tissue culture plastic and exposed to LPS (0.01 to 100 ng/ml). Expression of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) was subsequently determined by flow cytometry, a cDNA probe to canine ICAM-1 was used to quantify ICAM-1 mRNA, and changes in adhesion molecule function were assessed by evaluating the extent of homotypic aggregation. ICAM-1 and CD11a/CD18 were present on freshly isolated AMphis. CD11b/CD18 and CD11c/CD18 were expressed at lower levels. Nonadherent AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent cells. During short-term LPS stimulation (3 h), adherent AMphis increased both the synthesis and expression of ICAM-1. CD18 expression was either decreased or remained unchanged with LPS stimulation. LPS stimulation in vitro (> 0.01 ng/ml) enhanced the homotypic aggregation of adherent AMphis. Aggregation was blocked by monoclonal antibodies to ICAM-1 (CL18/6) and CD11a (R7.1) and CD18 (R15.7). Similar kinetics were found for expression of ICAM-1 and homotypic aggregation, suggesting that up-regulation of ICAM-1 is a major determinant of the LPS-stimulated aggregation of AMphis.

Animals↗
PubMed1993

P-selectin mediates spontaneous leukocyte rolling in vivo.

Rolling represents the initial step leading to leukocyte extravasation from blood vessels during an inflammatory reaction. In vitro studies indicate that P-selectin could be one of the ligands on endothelium involved in the rolling phenomenon, although the molecular determinants responsible for this transient attachment in vivo are still undefined. Our objectives were to develop a blocking monoclonal antibody against canine P-selectin and to use it to investigate the role of P-selectin in leukocyte rolling in vivo using the technique of intravital microscopy. P-selectin was immunoaffinity purified from canine platelets and used for the production of monoclonal antibodies. One of the hybridomas generated, MD6, was shown by enzyme-linked immunosorbent assay and by flow cytometry to bind preferentially to stimulated platelets and to completely prevent binding of stimulated platelets to neutrophils. Visualization of canine mesenteric venules by intravital microscopy showed that administration of MD6 resulted in a marked inhibition in the number of rolling leukocytes (18.96 +/- 9.92 v 156.40 +/- 19.50 leukocytes/min, P < .05; 88.3% +/- 6.0% inhibition). Control antibody MD3 (which recognizes a nonfunctional epitope of canine P-selectin) had no effect on the number of rolling leukocytes or on their rolling velocity. These results show for the first time that P-selectin plays an essential role in leukocyte rolling in vivo, and therefore may be a key participant of the inflammatory response.

Amino Acid Sequence↗
PubMed1993

Cytoplasmic Ca2+ does not inhibit the cardiac muscle sarcoplasmic reticulum ryanodine receptor Ca2+ channel, although Ca(2+)-induced Ca2+ inactivation of Ca2+ release is observed in native vesicles.

Single channel properties of cardiac and fast-twitch skeletal muscle sarcoplasmic reticulum (SR) release channels were compared in a planar bilayer by fusing SR membranes in a Cs(+)-conducting medium. We found that the pharmacology, Cs+ conductance and selectivity to monovalent and divalent cations of the two channels were similar. The cardiac SR channel exhibited multiple kinetic states. The open and closed lifetimes were not altered from a range of 10(-7) to 10(-3) M Ca2+, but the proportion of closed and open states shifted to shorter closings and openings, respectively. However, while the single channel activity of the skeletal SR channel was activated and inactivated by micromolar and millimolar Ca2+, respectively, the cardiac SR channel remained activated in the presence of high [Ca2+]. In correlation to these studies, [3H]ryanodine binding by the receptors of the two channel receptors was inhibited by high [Ca2+] in skeletal but not in cardiac membranes in the presence of adenine nucleotides. There is, however, a minor inhibition of [3H]ryanodine binding of cardiac SR at millimolar Ca2+ in the absence of adenine nucleotides. When Ca(2+)-induced Ca2+ release was examined from preloaded native SR vesicles, the release rates followed a normal biphasic curve, with Ca(2+)-induced inactivation at high [Ca2+] for both cardiac and skeletal SR. Our data suggest that the molecular basis of regulation of the SR Ca2+ release channel in cardiac and skeletal muscle is different, and that the cardiac SR channel isoform lacks a Ca(2+)-inactivated site.

Animals↗
PubMed1993

The calcium uptake of the rat heart sarcoplasmic reticulum is altered by dietary lipid.

Small amounts of dietary n-3 fatty acids can have dramatic physiological effects, including the reduction of plasma triglycerides and an elevation of cellular eicosapentanoic (EPA) and docosahexanoic acids (DHA) at the expense of arachidonic acid (AA). We investigated the effects of alterations in the fatty acid compositions of cardiac sarcoplasmic reticulum (CSR) produced by dietary manipulation on the calcium pump protein that is required for energy dependent calcium transport. CSR was isolated from rats fed menhaden oil, which is rich in n-3 fatty acids, and from control animals that were given corn oil. Relative to control membranes, those isolated from rats fed menhaden oil, had a lower content of saturated phospholipids, an increased DHA/AA ratio, and an increased ratio of n-3 to n-6 fatty acids. These changes were associated with a 30% decrease in oxalate-facilitated, ATP-dependent calcium uptake and concomitant decreased Ca-ATPase activity in the membranes from the animals fed menhaden oil. In contrast, there was no alteration in active pump sites as measured by phosphoenzyme formation. Thus, the CSR Ca-ATPase function can be altered by dietary interventions that change the composition, and possibly structure, of the phospholipid membranes thereby affecting enzyme turnover.

Adenosine Triphosphatases↗
PubMed1993

Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium.

Previous studies in vitro have shown an important role for intercellular adhesion molecule-1 (ICAM-1) in adherence interactions of canine neutrophils with canine jugular vein endothelial cells and in cytotoxicity of canine neutrophils for adult cardiac myocytes. To evaluate the regulation of ICAM-1 in myocardial inflammation and its role in the pathogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic administration of LPS elicited ICAM-1 mRNA in several tissues, including myocardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion and in both ischemic and normally perfused segments by 24 h of reperfusion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen thereafter as a function of time; (c) post-ischemic (but not preischemic) cardiac lymph collected at intervals from 1 to 24 h after reperfusion elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutrophil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular localization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.

Animals↗
PubMed1993

Production of a monoclonal antibody against canine GMP-140 (P-selectin) and studies of its vascular distribution in canine tissues.

Rapid upregulation of the adhesion molecule GMP-140 (P-selectin) on endothelial cells is believed to play an important role in the initial binding of leukocytes to endothelium, a very early step in the inflammatory response. Activated platelets that are involved in the coagulation system and in inflammatory processes also express GMP-140 on their surfaces. The objectives of the present study were to develop a monoclonal antibody against this adhesion molecule in the dog and to use this antibody to study platelet-neutrophil interactions in whole blood and to characterize the in vivo localization of GMP-140 in canine tissues. Five Balb/c mice were immunized with thrombin-stimulated dog platelets, and clones were screened using an enzyme-linked immunosorbent assay. The clone MD3 (IgG1) showed preferential binding to activated as compared with resting platelets. Flow cytometric analysis using MD3 revealed that 27% of circulating neutrophils in unstimulated blood had platelets bound to their surfaces; stimulation with platelet activating factor increased this percentage to 85%. Immunoblot analysis of solubilized dog platelets resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that the antibody MD3 recognized an approximately 140-kd protein. Immunohistochemical study of normal dog tissues with MD3 revealed that the antigen was present in endothelial cells of arteries, capillaries, and veins, depending on the specific tissue examined. Blood vessels staining positively with MD3 were most abundant in the digestive system (liver, stomach, small and large intestines), moderate in the lungs, kidneys, spleen, lymph nodes, and endocrine glands, and minimal in the brain, myocardium, skeletal system, and skin. Based on its presence on stimulated but not resting platelets, its molecular weight, and its vascular distribution, the antigen recognized by MD3 appears to be the selectin GMP-140 of the dog. This study documents that the cellular and tissue distribution of GMP-140 in dogs is very similar to that in human beings.

Animals↗