Biomedical subjects

Rachel L Matz

Publications and source records attributed to Rachel L Matz.

4 recordsLinked to original sources

PubMed2004

Promotion of leukocyte adhesion by a novel interaction between vitronectin and the beta2 integrin Mac-1 (alphaMbeta2, CD11b/CD18).

OBJECTIVE: The leukocyte integrin Mac-1 (alphaMbeta2, CD11b/CD18) binds a number of ligands and counter-receptors and thereby is a major determinant in regulation of leukocyte adhesion and extravasation. Vitronectin (VN) is an adhesion-promoting factor that is abundantly present as matrix molecule in vascular diseases such as atherosclerosis. Until now, only an indirect interaction between Mac-1 and VN via the urokinase receptor (urokinase plasminogen activator receptor) was known. We now propose that Mac-1 and VN can directly interact with each other. METHODS AND RESULTS: In an in vitro system with purified components, Mac-1 specifically bound the multimeric matrix form of VN but not the monomeric plasma form. Using various competitors, the interaction domains in Mac-1 and VN were localized. Mac-1-expressing but not untransfected Chinese hamster ovary cells adhered strongly on VN. Introduction of a GFFKR deletion in the alphaM subunit of Mac-1, which increases the constitutive activation of the integrin, led to increased adhesion on VN. Peripheral human blood neutrophils adhered and migrated on multimeric VN in a Mac-1-dependent manner. CONCLUSIONS: These results show that there is a specific integrin-affinity-regulated interaction between Mac-1 and the matrix form but not the plasma form of VN that may significantly participate in leukocyte adhesion and extravasation.

Animals↗

PubMed2003

Preservation of vascular contraction during ageing: dual effect on calcium handling and sensitization.

(1) The present study was aimed to characterize the effects of ageing on vascular contraction by noradrenaline in rat isolated arteries. The existence of vascular bed heterogeneity was investigated in endothelium-denuded conductance (aorta) and resistance (small mesenteric artery, SMA) arteries, with respect to Ca(2+) handling, Ca(2+) sensitization or Ca(2+)-independent mechanisms. (2) In both arteries, contractions to noradrenaline were not different between adult and aged rats. (3) In Ca(2+)- free medium, noradrenaline elicited a transient increase in tension that was reduced by the Ca(2+) mobilizing agents, ryanodine and thapsigargin, in arteries from adult rats. A loss of the thapsigargin- but not the ryanodine-sensitive component of noradrenaline-induced contraction was observed in the two arteries from aged rats. (4) After depletion of Ca(2+) stores with noradrenaline, addition of exogenous CaCl(2) produced a sustained contraction that was decreased to the same extent by the protein kinase C inhibitor, GF 109203X and the tyrosine kinase inhibitor, tyrphostin A-23, in arteries from adult and aged rats. The Rho-associated protein kinase inhibitor, Y-27632, caused identical relaxation of noradrenaline pre-contracted arteries from both age groups. (5) Basal intracellular calcium ([Ca(2+)](i)) was higher in SMA from aged than from adult rats. In addition, the noradrenaline [Ca(2+)](i)-force relationship was significantly shifted to the right in the SMA from aged rats. (6) Altogether, these data indicate that responsiveness to noradrenaline is preserved both in conductance and resistance arteries with ageing. The latter results from the association of increased basal [Ca(2+)](i), changes in Ca(2+) handling at the level of thapsigargin-sensitive sarcoplasmic reticulum Ca(2+)-ATPases and decreased myofilament sensitivity to Ca(2+).

Aging↗

PubMed2003

Intermolecular contact regions in urokinase plasminogen activator receptor.

The glycolipid-anchored urokinase-type plasminogen activator receptor (uPAR) is engaged in various signal transduction events related to cell adhesion, migration and proliferation. In this study, using phage display and peptide array techniques, we have identified several intermolecular contact regions of uPAR. Phage-displayed uPAR fragments bound to immobilized soluble uPAR on magnetic beads, revealing that regions uPAR-(7-28) and uPAR-(60-91) in domain I, uPAR-(101-121) in domain II and uPAR-(240-260) in domain III are possible uPAR-uPAR contact sites. Using peptide array, two additional sites could be identified, uPAR-(51-59) in domain I and uPAR-(144-155) in domain II. The putative uPAR-uPAR interaction sites are different from the previously identified uPA-binding sites. Functionally, peptides uPAR-(84-95) and uPAR-(240-248) could partially inhibit differentiated human U937 monocyte adhesion to vitronectin in the presence of uPA, indicating that these two uPAR regions might be involved not only in uPAR-uPAR but also in uPAR-vitronectin interactions. We propose that multiple uPAR-uPAR ectodomain interactions contribute considerably to the regulation of various cellular functions of uPAR.

Amino Acid Sequence↗

PubMed2003

Age-related endothelial dysfunction : potential implications for pharmacotherapy.

Aging per se is associated with abnormalities of the vascular wall linked to both structural and functional changes that can take place at the level of the extracellular matrix, the vascular smooth muscle and the endothelium of blood vessels. Endothelial dysfunction is generally defined as a decrease in the capacity of the endothelium to dilate blood vessels in response to physical and chemical stimuli. It is one of the characteristic changes that occur with age, independently of other known cardiovascular risk factors. This may account in part for the increased incidence of cardiovascular events in elderly people that can be reversed by restoring endothelial function. A better understanding of the mechanisms involved and the aetiopathogenesis of this process will help in the search for new therapeutic agents.Age-dependent alteration of endothelium-dependent relaxation seems to be a widespread phenomenon both in conductance and resistance arteries from several species. In the course of aging, there is an alteration in the equilibrium between relaxing and contracting factors released by the endothelium. Hence, there is a progressive reduction in the participation of nitric oxide and endothelium-derived hyperpolarising factor associated with increased participation of oxygen-derived free radicals and cyclo-oxygenase-derived prostanoids. Also, the endothelin-1 and angiotensin II pathways may play a role in age-related endothelial dysfunction. The use of drugs acting at different levels of these signalling cascades, including antioxidant therapy, lipid-lowering drugs and estrogens, seems to be promising.

Adult↗