Biomedical subjects

K A Aziz

Publications and source records attributed to K A Aziz.

8 recordsLinked to original sources

PubMed2001

Regulation of polymorphonuclear leukocyte function by platelets.

OBJECTIVE: To investigate the full effect of platelet-derived constituents on various polymorphonuclear neutrophil leukocyte responses. METHODS: Polymorphonuclear neutrophil leukocytes and platelets were separated from fresh blood of normal healthy volunteers. Platelets were then stimulated partially, or maximally to release constituents of their a- or a- and dense granules. The effects of these constituents on polymorphonuclear neutrophil leukocyte function (oxidase activity, degranulation and migration) were investigated. RESULTS: Platelet-derived constituents were found to both enhance, and inhibit polymorphonuclear neutrophil leukocytes-oxidant production, depending on the incubation time. Enhancement was due to dense granule-derived nucleotides (adenosine diphosphate and adenosine diphosphate), while inhibition was due to adenosine monophosphate derived from these nucleotides by polymorphonuclear neutrophil leukocyte surface nucleotidases. This latter inhibitory effect was reversed by the cytokine, granulocyte-macrophage colony stimulating-factor. Moreover, platelet constituents consistently enhanced other polymorphonuclear neutrophil leukocyte responses including degranulation and migration regardless of the incubation period. The latter enhancement was due to a-granule constituents, most likely platelet factor 4. CONCLUSION: Platelets, through release of their granular constituents, are able to modulate polymorphonuclear neutrophil leukocyte function in a way that is physiologically beneficial.

Blood Platelets↗

PubMed2000

Involvement of CD44-hyaluronan interaction in malignant cell homing and fibronectin synthesis in hairy cell leukemia.

The tissue homing of malignant hematic cells has both diagnostic and pathogenetic importance. Although such homing is incompletely understood, it generally involves cell adhesion and migration mediated by a number of adhesion receptors and cytokines. In this article, the potential importance of hyaluronan (HA) is examined for the tissue homing of hairy cells (HCs) in hairy cell leukemia (HCL). It is shown that HCs readily adhere to, and spontaneously move on, HA-coated surfaces using CD44. This indicates that activated CD44 and spontaneous movement on HA form part of the intrinsically activated phenotype of HCs. Interleukin-8 (IL-8) inhibited HC movement on HA, and this cell arrest was accompanied by increased actin polymerization and a more pronounced association of CD44 with the cytoskeleton. All of these findings are in sharp contrast to our previous observations with chronic lymphocytic leukemia cells, which are nonmotile on HA, but in response to IL-8 become polarized and motile using the receptor for HA-mediated motility rather than their apparently inactive CD44. Immunohistochemical examination of HCL tissues showed the ubiquitous presence of IL-8 and the prominence of HA in bone marrow stroma and hepatic portal tracts. This suggests that CD44-HA interactions are important in HC homing to these sites, but not to splenic red pulp or hepatic sinusoids, where HA is largely absent. Moreover, engagement of CD44 on HCs stimulates fibronectin synthesis, an observation that is likely to be relevant to the restriction of fibrosis in the disease to HC-infiltrated areas containing HA.

Cell Adhesion↗

PubMed2000

Activation-dependent proteolytic degradation of polymorphonuclear CD11b.

CD11b/CD18 is the principal integrin of polymorphonuclear (PMN) leucocytes and is involved in their adhesion, migration and phagocytosis. In quiescent cells, the receptor is stored in intracellular granules from where it is translocated to the cell surface in response to a variety of stimuli. In this study, we demonstrated that strong stimulation of PMNs not only leads to the upregulation of CD11b surface expression, but also to the subsequent time-dependent apparent loss of this receptor, as detected by fluorescence-activated cell sorting (FACS) using a monoclonal antibody (mAb) against an N-terminal CD11b epitope. This epitope loss was observed following either direct stimulation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) or after multiple receptor stimulation using a combination of the agonist N-formylmethionyl-leucyl-phenylalanine (FMLP) and the priming agents granulocyte macrophage-colony stimulating factor (GM-CSF) and platelet factor (PF) 4. However, upregulation following weak stimulation with FMLP alone was not followed by subsequent epitope loss of the receptor. The increases and subsequent decreases in CD11b expression induced by PMA were paralleled by an increase and a decrease in PMN adhesion to CD11b-specific ligands, fibrinogen and intercellular adhesion molecule (ICAM)-1. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis showed that this epitope loss of PMN CD11b was the result of proteolytic degradation of the N-terminal region of the molecule. The use of a range of proteinase inhibitors indicated that this CD11b degradation involves a cell-associated serine proteinase. This is the first demonstration of the proteolytic alteration of CD11b in response to strong PMN stimulation. Given the central role of CD11b/CD18 in all aspects of PMN function, this alteration of the CD11b molecule and its effect on PMN adhesion are probably of considerable pathophysiological importance.

Antibodies, Monoclonal↗

PubMed1997

Sequential potentiation and inhibition of PMN reactivity by maximally stimulated platelets.

In a recent study, we showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and supernatants from partially stimulated platelets undergoing selective alpha-granule release synergistically enhanced polymorphonuclear leukocyte (PMN) response to N-formyl-methionyl-leucyl-phenylalanine (fMLP). The active factor released from platelet alpha-granules was identified as platelet factor four (PF4). In this study we investigate the joint effect on PMN reactivity of GM-CSF and supernatants from platelets maximally stimulated to release both alpha- and dense granule contents. These platelet supernatants enhanced PMN chemiluminescence (CL; a measure of the oxidative burst) during short incubations, whereas longer incubations led to the loss of this enhancement and the prevention of PMN priming by GM-CSF. The platelet-derived inhibitory factor was of low molecular weight, originated from the dense granule precursor(s), and its generation required the presence of PMN. When ATP/ADP were incubated with PMN at concentrations found in platelet-dense granules, they produced a similar biphasic effect on PMN reactivity (a potentiation followed by inhibition) as seen with the platelet supernatants. The inhibitory effect of these nucleotides coincided with their conversion to AMP. AMP per se had an immediate inhibitory effect on PMN response to fMLP and prevented PMN priming by GM-CSF. This study confirms that partially stimulated platelets enhance PMN reactivity. However, during maximal stimulation, nucleotides released from the platelet-dense granules are converted to AMP, which in turn can counteract the PMN priming effects of factors such as PF4 and GM-CSF.

Adenosine Diphosphate↗

PubMed1995

Degradation of platelet glycoprotein Ib by elastase released from primed neutrophils.

Mutual interactions between neutrophils (PMN) and platelets are recognized to be important in modulating the respective functions of these two cell types. Here we show that primary granule secretion from appropriately-stimulated PMN can lead to complete proteolytic removal of GPIb from the platelet surface. Thus, when the PMN in PMN/platelet mixtures were stimulated by FMLP, platelets lost GPIb as measured by ristocetin-induced aggregation, flow cytometry and SDS-PAGE analysis. This loss was most marked when PMN were primed by GM-CSF, and could be inhibited by a specific elastase inhibitor. As expected, the alpha 1-antiproteinase in plasma inhibited GPIb loss, but when PMN were strongly stimulated by FMLP and GM-CSF in the presence of platelets this inhibition was incomplete or absent. It is concluded that joint priming of PMN with GM-CSF and platelets can cause a previously unrecognized degree of primary granule secretion which, via elastase, leads to platelet GPIb loss. We suggest that this loss is likely to be of physiological and pathophysiological importance.

Blood Platelets↗

PubMed1995

Platelets prime PMN via released PF4: mechanism of priming and synergy with GM-CSF.

Platelet-PMN interactions have been extensively studied and a spectrum of possible effects has been demonstrated. However, the physiological relevance of many of the observed in vitro phenomena remains obscure. Here we report a novel, and potentially pathophysiologically important, mechanism by which platelets can enhance PMN reactivity. We first observed that addition of platelets to PMN suspensions enhanced the chemiluminescence response of PMN to FMLP. This enhancement occurred without augmentation of superoxide generation and did not involve mutual platelet-PMN adhesion. The soluble material responsible was biochemically and immunologically identified as PF4 derived from platelet alpha-granules. The alpha-granule release was shown to be selective and required minimal platelet stimulation. Since the PF4 effect did not influence NADPH oxidase activation, it differed markedly from that of other priming agents such as GM-CSF. Further studies showed that the PF4 effect was attributable entirely to the surface translocation and secretion of primary granule myeloperoxidase. There was marked synergy between PF4 and GM-CSF and both were required for maximal potentiation of PMN reactivity. These results demonstrate that PF4 and GM-CSF employ different pathways in PMN priming. The ease with which platelets could release PF4 at sites of vessel-wall damage and inflammation suggests that platelet-PMN interaction via PF4 is likely to be of major pathophysiological importance.

Blood Platelets↗

PubMed1994

The role of G-CSF in mature neutrophil function is not related to GM-CSF-type cell priming.

Because of uncertainties regarding the comparability of granulocyte-macrophage and granulocyte colony-stimulating factors with regard to their effects on mature neutrophils (PMNs), we compared the actions of the two cytokines on reactive oxidant production and granular secretion by these cells. We found that chemiluminescence (CL) stimulated by formylmethionyl-leucyl-phenylalanine (fMLP) was not influenced by G-CSF (0.1-100 ng/ml), whereas GM-CSF priming (10 ng/ml) caused a nearly twofold increase in this PMN response. Moreover, the reactivity of PMNs treated with GM-CSF and G-CSF in combination was not different from that of PMNs treated with GM-CSF alone. GM-CSF (10 ng/ml) increased the rate of O2- production by 79%, caused a fivefold increase in fMLP-induced myeloperoxidase (MPO) secretion, and strongly enhanced CD11b expression. In contrast, G-CSF (50 ng/ml) only slightly increased O2- production (by 15%), and MPO secretion and CD11b expression remained unchanged. Both cytokines together gave results similar to those obtained with GM-CSF alone. In the presence of platelets (which by themselves enhanced PMN reactivity), the differences in the effects of the two cytokines persisted. We conclude that the priming effect of G-CSF on mature PMNs is negligible compared with that of GM-CSF. Our results are in conflict with previous reports of much more pronounced G-CSF effects but in accord with recent work showing the failure of this cytokine to induce a range of effects produced by GM-CSF. We therefore suggest that the primary role of G-CSF in mature PMN function is still unclear but may be related to the control of PMN distribution in view of the mobilizing and marginating effects of the cytokine in vivo.

Antigens, CD↗

PubMedDate not supplied

Three cases of dural arteriovenous fistula of the anterior condylar vein within the hypoglossal canal.

Dural arteriovenous fistulas (DAVFs) of the anterior condylar vein are an uncommon but important subset of fistulas occurring at the skull base that can be confused with DAVFs of the marginal sinus on angiography. MR angiography source images can document the intraosseous extent and the relationship to the hypoglossal canal of this type of fistula, which can have significant clinical implications. We present the imaging features of angiography, CT, and MR angiography of three cases of DAVFs localized to the anterior condylar vein and within the hypoglossal canal, which were confirmed by source images from MR angiography. Transvenous coil embolization was curative in two of three cases and would seem to be the treatment of choice when venous access is available.

Aged↗