PubMed Health⌕ Search

Biomedical subjects

L W Argenbright

Publications and source records attributed to L W Argenbright.

13 recordsLinked to original sources
PubMed1997

Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators.

The objective of this study was to define the role of oxidants and lipid mediators in the leukocyte-endothelial cell adhesion and albumin leakage elicited in rat mesenteric venules by ischemia-reperfusion (I/R). Intravital fluorescence microscopy was used to monitor leukocyte adherence and emigration, platelet-leukocyte aggregation, mast cell degranulation, and albumin leakage after release of a 20-min arterial occlusion. I/R elicited large increases in leukocyte-endothelial cell adhesion and albumin leakage. These responses were significantly attenuated in venules treated with either superoxide dismutase, oxypurinol (an inhibitor of xanthine oxidase), lodoxamide (a mast cell stabilizer), WEB-2086 (a platelet-activating factor antagonist), or SC-41930 (a leukotriene B4-receptor antagonist) but not by U-74006F (an inhibitor of lipid peroxidation). Platelet-leukocyte aggregates and mast cell degranulation induced by I/R were also attenuated by administration of either superoxide dismutase or lodoxamide. These results support the hypothesis that oxidants produced, in part, by xanthine oxidase promote the formation (by mast cells and endothelial cells) of platelet-activating factor and leukotriene B4, which recruit and activate leukocytes in postischemic venules. The adherent and emigrated leukocytes then mediate the increased albumin extravasation observed in the postcapillary venules.

Animals↗
PubMed1997

Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and hypercholesterolemic rats.

The objective of this study was to define the influence of hypercholesterolemia on ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules. The microvascular alterations normally elicited by I/R (leukocyte adherence and emigration, albumin leakage, and platelet aggregation) were more pronounced in hypercholesterolemic rats (compared with control rats). Monoclonal antibodies against the adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 attenuated the I/R-induced leukocyte adherence and emigration and albumin leakage. Leukocyte adherence, but not albumin leakage, was diminished in animals pretreated with a P-selectin-specific antibody. Platelet aggregation was reduced by antibodies directed against either P-selectin, CD18, or intercellular adhesion molecule-1, as well as a GPIIb-IIIa antagonist. These results indicate that the enhanced reperfusion-induced albumin leakage in hypercholesterolemic rats is dependent on leukocyte-endothelial cell adhesion. Furthermore, P-selectin- and CD11/CD18-dependent heterotypic and GPIIb-IIIa-mediated homotypic platelet aggregation appear to influence the extravasation of both leukocytes and albumin in postischemic venules of hypercholesterolemic rats.

Animals↗
PubMed1996

Oxidative stress during platelet-activating factor-induced microvascular dysfunction.

OBJECTIVE: To assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte-endothelial cell adhesion and increased microvascular permeability (to fluorescein isothiocyanate [FITC]-albumin) observed in rat mesenteric venules exposed to platelet-activating factor (PAF). METHODS: The production of oxidants derived from H2O2 in mesenteric tissue was monitored using the H2O2-sensitive fluorochrome, dihydrorhodamine 123 (DHR). PAF elicited a rapid increase in both the albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules. RESULTS: The PAF-induced oxidation of DHR, leukocyte-endothelial cells interactions, and albumin leakage were attenuated by treatment with either catalase or dimethylthiourea. Treatment with monoclonal antibody directed against either CD11b/CD18 on leukocytes or ICAM-1 on endothelial cells attenuated the PAF-induced oxidative stress, albumin leakage, and leukocyte-endothelial cell adhesion. CONCLUSIONS: These findings indicate that most of the oxidants generated in mesenteric tissue exposed to PAF results from the accumulation of activated leukocytes.

Animals↗
PubMed1994

Role of adhesion glycoproteins CD18 and intercellular adhesion molecule-1 in complement-mediated reactions of rabbit skin.

1. The role of the adhesion glycoproteins CD18 and intercellular adhesion molecule-1 (ICAM-1) in inflammatory responses produced during a reversed passive Arthus (RPA) reaction and induced by zymosan and zymosan-activated plasma (ZAP) were studied in rabbit skin. 2. Oedema formation and haemorrhage were quantified by measuring accumulation of 125I-albumin and 111In-labelled red blood cells (111In-RBC) respectively. 3. Monoclonal antibody (mAb) R15.7 (anti-CD18), administered intravenously, abolished accumulation of 125I-albumin and 111In-RBC in dermal RPA reactions and in response to locally injected zymosan and ZAP. 4. When administered intravenously, the mAb RR1/1 (anti-ICAM-1) suppressed 125I-albumin and 111In-RBC accumulation in dermal RPA reactions and at sites treated with zymosan and ZAP. 5. Oedema formation in response to platelet-activating factor (PAF) and bradykinin (BK) either in the presence or absence of prostaglandin E2 (PGE2) were not affected by mAb R15.7 or by mAb RR1/1.1.1. 6. We conclude that oedema formation and haemorrhage associated with RPA reactions and in responses to zymosan and ZAP are completely CD18-dependent, and are mediated, at least in part, via ICAM-1. Responses to the neutrophil-independent oedema forming mediators, PAF and BK are not dependent upon CD18 or ICAM-1.

Animals↗
PubMed1992

Interactions of leukocyte integrins with intercellular adhesion molecule 1 in the production of inflammatory vascular injury in vivo. The Shwartzman reaction revisited.

We have investigated the role of leukocyte-endothelial cell interactions in a rabbit model of hemorrhagic vasculitis. Microvascular injury was produced in the skin by intradermal injection of Salmonella typhosa endotoxin followed 20 h later by intravenous zymosan, which activates complement. Hemorrhagic necrosis develops in the "prepared" skin sites which is characterized by microthrombi, neutrophil aggregation, platelet and fibrin deposition, and massive extravasation of erythrocytes. Hemorrhage in these Shwartzman-like lesions was quantitated by 99mTc-labeled autologous erythrocytes. Inhibition of the hemorrhagic response was obtained with mAb reactive with ICAM-1 as well as mAb against the leukocyte CD18 when either was administered intravenously just before intravenous zymosan challenge. This observation suggests that an intravascular event occurring in response to complement activation is required for the development of hemorrhagic vasculitis. We hypothesize that agents which successfully prepare the skin for the Shwartzman response after their intradermal injection do so by promoting increased intercellular adhesion molecule 1 (ICAM-1) expression on the vascular endothelium. Activation of complement then induces CD11/CD18 expression on circulating leukocytes thus producing an intravascular CD11/CD18-ICAM-1 (leukocyte-endothelium) adhesion event. Inhibition of intravascular leukocyte-leukocyte aggregation with mAb against CD11b (Mac-1) showed partial inhibition of hemorrhage, while mAb against CD11a (LFA-1) showed no inhibitory activity. This type of cytokine-primed, neutrophil-dependent vascular damage may be a model of human vasculitic processes where microvascular damage is produced in the absence of immune-complex deposition.

Animals↗
PubMed1991

Monoclonal antibodies to the leukocyte membrane CD18 glycoprotein complex and to intercellular adhesion molecule-1 inhibit leukocyte-endothelial adhesion in rabbits.

Increasing evidence indicates that leukocyte-endothelium adhesion is mediated, in part, by the CD11/CD18 family of heterodimeric glycoproteins expressed on the leukocyte plasma membrane and by intercellular adhesion molecule-1 (ICAM-1) which is expressed on endothelial cells. We have used the technique of intravital microscopy to visualize the microcirculation of the rabbit mesentery and to evaluate effects of antibodies against several adhesion glycoproteins on C5a-induced leukocyte adhesion. Addition of zymosan-activated serum (a source of C5a) to the buffer superfusing the mesenteric microvasculature induced rapid adhesion of leukocytes to the endothelium of post-capillary venules. Monoclonal antibodies R15.7 (anti-CD18), R7.1 (anti-CD11a, LFA-1), and R6.5 (anti-ICAM-1), administered intravenously before C5a exposure, strongly inhibited leukocyte adherence while antibody LM2 (anti-CD11b, Mac-1) produced significant, but weaker, inhibition. If these antibodies were administered after C5a-induced adhesion had begun, both R15.7 and R7.1 displaced adherent leukocytes and prevented further leukocyte accumulation: LM2 and R6.5 did not displace adherent leukocytes or inhibit incoming leukocytes from adhering. These data confirm earlier findings establishing a role for CD18 in leukocyte adhesion in vivo and extend those observations to implicate both CD11a and CD11b in that adhesion. In addition, we report that ICAM-1 mediates, in part, the initial leukocyte-endothelial cell adhesion following C5a exposure in vivo.

Animals↗
PubMed1991

The Shwartzman response: a model of ICAM-1 dependent vasculitis.

The local Shwartzman response was produced in rabbits by the intradermal injection of endotoxin, followed 24 h later by intravenous zymosan. Hemorrhagic lesions developed in the prepared skin sites. We quantitated the Shwartzman-induced hemorrhage with autologous 99mTc-erythrocytes. We show that the development of the Shwartzman response depends on both leukocyte membrane CD18 glycoprotein activity as well as the participation of intercellular adhesion molecule-1 (ICAM-1). We discuss the possibility that the common property shared by the agents capable of preparing the skin for the Shwartzman response is the ability to induce ICAM-1 expression.

Animals↗
PubMed1989

An enzymatic method for distinguishing the stereoisomers of 12-hydroxyeicosatetraenoic acid in human epidermis and psoriatic scale.

Homogenates of normal human epidermis synthesized 12-hydroxyeicosatetraenoic acid (12-HETE) when incubated in vitro with arachidonic acid. The stereoconfigurations of the C-12 hydroxyl isomers were determined by incubation with potato 5-lipoxygenase. The synthesized substrate-specific diHETEs; 5S, 12R and 5S, 12S, were readily separated by high performance liquid chromatography. Using this novel methodology, the normal epidermis was found to synthesize predominantly 12-S-HETE while, in contrast, psoriatic scale was found to contain 12-R-HETE. The 5-lipoxygenase inhibitors, Merck L-651, 896, Takeda AA86I, and the active metabolite of Syntex lonapalene were found to inhibit 12-HETE formation in normal epidermal homogenates.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Assessment of gastric bleeding in rats: effects of cyclooxygenase inhibitors and 16,16-dimethyl prostaglandin E2 on gastric bleeding.

Gastric bleeding caused by cyclooxygenase inhibitors has been assessed by a novel method. Rats are adapted to a strict light-dark cycle with limited access to food to reduce the stress associated with starvation. Such animals are then labeled with 51Cr-red blood cells from donor animals and dosed with the compound under evaluation. After 24 hr. animals are sacrificed and the amount of blood that has accumulated in the lumen of the cecum is quantitated. The potency of cyclooxygenase inhibitors in this assay to cause gastric bleeding is as follows: indomethacin greater than piroxicam greater than naproxen greater than ibuprofen greater than diflunisal which is similar to their antiinflammatory potency in the rat. In addition, the protective activity of PGE2 on indomethacin-induced gastric bleeding is clearly shown by this method.

16,16-Dimethylprostaglandin E2↗
PubMed1982

Erythema and skin blood content.

We have studied the inflammatory response produced by painting pigs and hairless mice with anthracene and subsequently exposing the skin to fluorescent blacklight lamps. Erythema and oedema appeared in pig skin shortly after the onset of irradiation; oedema but no erythema was evident in mouse skin. The response in both animals became increasingly severe as long as irradiation continued, and began to resolve when irradiation ceased. Hyperaemia (increased tissue blood content) was quantified by the increased in 51Cr-RBC content (c.p.m./wet weight) of the skin. Erythema (appearance of redness) was assessed by the use of an 'erythema grading scale' consisting of red gelatin filters of increased red saturation sandwiched between clear acrylic sheets. Mouse skin responded with a nine-fold hyperaemia compared with unirradiated skin, although no erythema was produced. In contrast, pig skin responded with intense erythema with no corresponding increase in hypaeremia. It is apparent that a stimulus which produced hyperaemia will not necessarily produced erythema, and erythema can develop without hyperaemia.

Animals↗
PubMed1980

Quantitation of phototoxic hyperemia and permeability to protein: II. Inhibition by histamine (H1 and H2) receptor antagonists in mouse skin.

Exposure of anthracene treated skin to long-wave ultraviolet radiation (UVA) will produce hyperemia, increased vascular permeability, burning and itching. This photosensitized inflammation was produced in the skin of hairless mice by the topical application of a 0.025% (w/v) solution of anthracene followed by exposure to UVA. The resultant hyperemia was quantified by the increase in 51Cr-erythrocyte content (cpm/wet weight) of skin. After 1000 sec (1.3 x 10(4)J/M2) of UVA, the blood content of the skin had increased nine-fold. Pyrilamine (H1 antagonist), administered orally, did not inhibit the hyperemia in response to anthracene-UVA, whereas cimetidine (H2 antagonist) increased the blood content of the skin. However, a combination of pyrilamine and cimetidine significantly inhibited the hyperemia, indicating that histamine may mediate the anthracene-UVA hyperemia via H1 and H2 receptors on dermal vessels. Since neither antagonist alone blocked the response, the mechanism of histamine action in this response may involve histamine receptors on other dermal components in addition to the blood vessels. In particular, the exacerbation of this photosensitized inflammation by cimetidine lends support to the concept of H2 receptors on mast cells which negatively modulate histamine release.

Animals↗
PubMedDate not supplied

Cephalosporin antibiotics can be modified to inhibit human leukocyte elastase.

Several laboratories, including our own have reported the synthesis and activity of certain low relative molecular mass inhibitors of mammalian serine proteases, especially human leukocyte elastase (HLE, EC 3.4.21.37), an enzyme whose degradative activity on lung elastin has been implicated as a major causative factor in the induction of pulmonary emphysema, and which is present in the azurophil granules of human polymorphonuclear leukocytes (PMN). Normally, these granules fuse with phagosomes containing engulfed foreign material (such as bacteria), and HLE, in combination with other lysosomal enzymes, catabolizes the particles. Under certain pathological conditions, however, PMN become attached to host protein (elastin fibres, basement membrane, connective tissue, immune complexes), and in response to this adherence, the granules may fuse with the PMN outer membrane and release their contents, including HLE, directly onto the tissue. Besides emphysema, HLE may also contribute to the pathogenesis of disease states such as adult respiratory distress syndrome, and its potential involvement in rheumatoid arthritis makes HLE inhibitors of considerable interest. It is known that cephalosporin antibiotics (for example, cephalothin (compound I, Table 2)) are acylating inhibitors of bacterial serine proteases which help synthesize the cell wall by performing a transpeptidation reaction on a peptidyl substrate bearing a D-Ala-D-Ala terminus. We now report that neutral cephalosporins (that is, compounds not bearing a free carboxyl at position C-4) can be modified to become potent time-dependent inhibitors of HLE.

Cephalosporins↗