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Majeed, Meytham
Alternative names
Publications (10 of 15) Show all publications
Kälvegren, H., Majeed, M. & Bengtsson, T. (2003). Chlamydia pneumoniae binds to platelets and triggers P-selectin expression and aggregation: A causal role in cardiovascular disease?. Arteriosclerosis, Thrombosis and Vascular Biology, 23(9), 1677-1683
Open this publication in new window or tab >>Chlamydia pneumoniae binds to platelets and triggers P-selectin expression and aggregation: A causal role in cardiovascular disease?
2003 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 23, no 9, p. 1677-1683Article in journal (Refereed) Published
Abstract [en]

Objective - Evidence linking Chlamydia pneumoniae to atherosclerotic cardiovascular disease is expanding. Platelets are considered to play an essential role in cardiovascular diseases, however, so far platelets have not been associated with an infectious cause of atherosclerosis. This study aims to clarify the interaction between Cpneumoniae and platelets and possibly present a novel mechanism in the pathogenesis of atherosclerosis.

Methods and Results - The effects of C pneumoniae on platelet aggregation and secretion were assessed with lumiaggregometry, and the ability of C pneumoniae to bind to platelets and stimulate expression of P-selectin was analyzed with flow cytometry. We found that Cpneumoniae, at a chlamydia:platelet ratio of 1:15, adheres to platelets and triggers P-selectin expression after 1 minute and causes an extensive aggregation and ATP secretion after 20 minutes of incubation. Inhibition of glycoprotein IIb/IIIa with Arg-Gly-Asp-Ser or abciximab markedly reduced C pneumoniae-induced platelet aggregation. Exposure of C pneumoniae to polymyxin B, but not elevated temperature, abolished the stimulatory effects on platelet activation, suggesting that chlamydial lipopolysaccharide has an active role. In contrast, other tested bacteria had no or only moderate effects on platelet functions.

Conclusion - Our findings demonstrate a new concept of how C pneumoniae activates platelets and thereby may cause atherosclerosis and thrombotic vascular occlusion.

 

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14386 (URN)10.1161/01.ATV.0000084810.52464.D5 (DOI)
Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2017-12-13Bibliographically approved
Nimeri, G., Majeed, M., Elwing, H., Öhman, L., Wetterö, J. & Bengtsson, T. (2003). Oxygen radical production in neutrophils interacting with platelets and surface-immobilized plasma proteins: role of tyrosine phosphorylation. Journal of Biomedical Materials Research, 67A(2), 439-447
Open this publication in new window or tab >>Oxygen radical production in neutrophils interacting with platelets and surface-immobilized plasma proteins: role of tyrosine phosphorylation
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2003 (English)In: Journal of Biomedical Materials Research, ISSN 0021-9304, E-ISSN 1097-4636, Vol. 67A, no 2, p. 439-447Article in journal (Refereed) Published
Abstract [en]

The interaction between neutrophil granulocytes and platelets is considered to play an important role in the inflammatory process induced by an implanted foreign material. However, the cellular mechanisms involved remain incompletely understood. We used a luminol-dependent chemiluminescence (CL) technique to analyze the generation of reactive oxygen species (ROS) in human neutrophils interacting with different plasma protein-coated surfaces in the presence or absence of unstimulated or stimulated platelets. The role of tyrosine phosphorylation in the regulation of NADPH oxidase activity was evaluated with quantitative fluorescence microscopy and the specific tyrosine kinase inhibitor genistein. We found that the ROS-production is 2 to 3 times higher in neutrophils on immunoglobulin G (IgG)coated surfaces than in cells interacting with albumin- or fibrinogen-coated surfaces. Incubation with superoxide dismutase and catalase revealed that about 45% of the ROS was released extracellularly on IgG surfaces whereas corresponding values were 90% and 85% in neutrophils interacting with albumin and fibrinogen, respectively. The presence of platelets markedly increased the extracellular generation of ROS, mainly in neutrophils. interacting with IgG- or fibrinogen-coated surfaces whereas the intracellular production was only modestly affected. Quantitative fluorescence microscopy of neutrophils stained with FITC-conjugated anti-phosphotyrosine antibodies showed a correlation between tyrosine phosphorylation, cell spreading, and ROS production. Platelets markedly amplified the anti-phosphotyrosine staining on both fibrinogen- and IgG-coated surfaces whereas the low level of tyrosine phosphorylation in neutrophils on albumin-coated surfaces was not further elevated by platelets. Furthermore, the tyrosine kinase inhibitor genistein inhibited both extra- and intracellular ROS production in neutrophils regardless of the presence of platelets. We demonstrate that plasma protein coating and the presence of platelets are crucial for the inflammatory response of adhering neutrophils and that the oxidative response correlates with the extent of tyrosine phosphorylation of proteins in focal contacts. (C) 2003 Wiley Periodicals, Inc.

Keywords
plasma protein, neutrophil, platelet, reactive oxygen species, tyrosine phosphorylation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-47746 (URN)10.1002/jbm.a.10081 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Majeed, M., Caveggion, E., Lowell, C. & Berton, G. (2001). Role of Src kinases and Syk in Fc? receptor-mediated phagocytosis and phagosome-lysosome fusion. Journal of Leukocyte Biology, 70(5), 801-811
Open this publication in new window or tab >>Role of Src kinases and Syk in Fc? receptor-mediated phagocytosis and phagosome-lysosome fusion
2001 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 70, no 5, p. 801-811Article in journal (Refereed) Published
Abstract [en]

Phagocytosis is increased by Fc? receptors (Fc?Rs), and studies with syk-1- macrophages demonstrated that Syk kinase is required for Fc?TR phagocytosis. Similar studies with macrophages lacking the Src family kinases Hck, Fgr, and Lyn showed that these kinases are not required for phagocytosis but that they enhance the rate of particle engulfment. In this report we show that both wild-type and hck-1- fgr-1- macrophages expressed Fyn, Src, and Yes and that these kinases were activated on ingestion of immunoglobulin G (IgG)-coated particles and redistributed, together with Syk, to actin-rich phagocytic cups and the phagosomal membrane. At doses blocking IgG-dependent phagocytosis, the tyrosine kinase inhibitors PP1 and piceatannol inhibited both Src family kinase and Syk activities, as well as their redistribution to actin-rich phagocytic cups. Hck, Fgr, and Lyn were dispensable for lysosome-phagosome fusion (PLF) induced by IgG-coated particles. However, PP1 or piceatannol hampered unopsonized yeast-induced PLF despite the fact that they did not block yeast internalization.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26057 (URN)10516 (Local ID)10516 (Archive number)10516 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
Ydrenius, L., Majeed, M., J Rasmusson, B., Stendahl, O. & Särndahl, E. (2000). Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis. Journal of Leukocyte Biology, 67(4), 520-528
Open this publication in new window or tab >>Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis
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2000 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 67, no 4, p. 520-528Article in journal (Refereed) Published
Abstract [en]

We have investigated the role of cAMP and cAMP-dependent protein kinase (cAPK) in neutrophil phagocytosis. Inhibition of cAPK with H-89 reduced complement- and IgG-dependent phagocytosis to 83 and 46%, respectively. Fluorescence intensity measurements of phalloidin-stained actin in neutrophils showed a reduced amount of filamentous actin (F-actin) in pseudopods and around the phagosome in cells treated with H-89 or cAMP-elevating agents (forskolin and rolipram). The amount of phosphotyrosine-containing proteins was also reduced in pseudopods and around the phagosome. Taken together, the data show that cAMP/cAPK regulates F-actin reorganization during receptor-mediated phagocytosis, particularly triggered by IgG-FcR interaction. Our results support the hypothesis that active subcortical reorganization of F-actin is a prerequisite for FcR-mediated phagocytosis, but is less important during CR3-mediated ingestion.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25401 (URN)9844 (Local ID)9844 (Archive number)9844 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Constantin, G., Majeed, M., Giagulli, C., Piccio, L., Kim, J., Butcher, E. & Laudanna, C. (2000). Chemokines trigger immediate beta2 integrin affinity and mobility changes: Differential regulation and roles in lymphocytes arrest under flow.. Immunity, 13, 759-769
Open this publication in new window or tab >>Chemokines trigger immediate beta2 integrin affinity and mobility changes: Differential regulation and roles in lymphocytes arrest under flow.
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2000 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 13, p. 759-769Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26056 (URN)10515 (Local ID)10515 (Archive number)10515 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
Majeed, M., Krause, K.-H., Clark, R., Kihlström, E. & Stendahl, O. (1999). Localization of intracellular Ca2+ stores in HeLa cells during infection with Chlamydia trachomatis. . Journal of Cell Science, 112, 35-44
Open this publication in new window or tab >>Localization of intracellular Ca2+ stores in HeLa cells during infection with Chlamydia trachomatis. 
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1999 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 112, p. 35-44Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25991 (URN)10443 (Local ID)10443 (Archive number)10443 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
Andersson, K., Magnusson, K.-E., Majeed, M., Stendahl, O. & Fällman, M. (1999). Yersinia pseudotuberculosis-induced calcium signaling in neutrophils is blocked by the virulence effector YopH. Infection and Immunity, 67(5), 2567-2574
Open this publication in new window or tab >> Yersinia pseudotuberculosis-induced calcium signaling in neutrophils is blocked by the virulence effector YopH
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1999 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 67, no 5, p. 2567-2574Article in journal (Refereed) Published
Abstract [en]

Pathogenic species of the genus Yersinia evade the bactericidal functions of phagocytes. This evasion is mediated through their virulence effectors, Yops, which act within target cells. In this study we investigated the effect of Yersinia pseudotuberculosis on Ca 2+ signaling in polymorphonuclear neutrophils. The intracellular free calcium concentration in single adherent human neutrophils was monitored during bacterial infection and, in parallel, the encounter between the bacteria and cells was observed. When a plasmid-cured strain was used for infection, adherence of a single bacterium to the cellular surface induced a β 1 integrin-dependent transient increase in the intracellular concentration of free calcium. This was, however, not seen with Yop-expressing wild-type bacteria, which adhered to the cell surface without generating any Ca 2+ signal. Importantly, the overall Ca 2+ homeostasis was not affected by the wild-type strain; the Ca 2+ signal mediated by the G-protein-coupled formyl-methionyl-leucyl- phenylalanine receptor was still functioning. Hence, the blocking effect was restricted to certain receptors and their signaling pathways. The use of different Yop mutant strains revealed that the protein tyrosine phosphatase YopH was responsible for the inhibition. This virulence determinant has previously been implicated in very rapid Yersinia-mediated effects on target cells as the key effector in the blockage of phagocytic uptake. The present finding, that Y. pseudotuberculosis, via YopH, specifically inhibits a self- induced immediate-early Ca 2+ signal in neutrophils, offers more-detailed information concerning the effectiveness of this virulence effector and implies an effect on Ca 2+-dependent, downstream signals.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25766 (URN)10200 (Local ID)10200 (Archive number)10200 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
Majeed, M., Perskvist, N., Ernst, J. D., Orselius, K. & Stendahl, O. (1998). Roles of calcium and annexins in phagocytosis and elimination of an attenuated strain of Mycobacterium tuberculosisin human neutrophils. Microbial Pathogenesis, 24(5), 309-320
Open this publication in new window or tab >>Roles of calcium and annexins in phagocytosis and elimination of an attenuated strain of Mycobacterium tuberculosisin human neutrophils
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1998 (English)In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 24, no 5, p. 309-320Article in journal (Refereed) Published
Abstract [en]

The phagocytic function of neutrophils is a crucial element in the host defence against invading microorganisms. We investigated phagocytosis and intracellular killing of an attenuated strain of Mycobacterium tuberculosis(H37Ra) by human neutrophils focusing on the role of the cytosolic free calcium concentration [Ca2+]iand certain cytosolic calcium-dependent membrane-binding proteins annexins. Phagocytic uptake did not trigger a calcium rise and occurred independently of different calcium conditions, and in a serum-dependent manner. Changes in the viability of H37Ra were determined by agar plate colony count and a radiometric assay. Neutrophils showed a capacity to kill ingested mycobacteria and this occurred without a rise in [Ca2+]i. The ability to kill H37Ra decreased in the absence of extracellular calcium and when intra-extracellular calcium was reduced. Immunofluorescence staining revealed that during phagocytosis of H37Ra, annexins III, IV and VI translocated from cytoplasm to the proximity of the H37Ra-containing phagosomes, whereas the localization of annexin I and V remained unchanged. The translocation of annexin IV occurred even when Ca2+-depleted neutrophils ingested H37Ra in the absence of extracellular calcium. We concluded that neutrophil-mediated killing of mycobacteria is a Ca2+-dependent process. The fact that the association of certain annexins to the membrane vesicle containing H37Ra differ from other phagosomes suggests a selective regulatory mechanism during phagocytosis of mycobacteria by neutrophils.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81105 (URN)10.1006/mpat.1997.0200 (DOI)
Available from: 2012-09-07 Created: 2012-09-07 Last updated: 2017-12-07Bibliographically approved
Zimmerli, S., Majeed, M., Gustafsson, M., Stendahl, O., Sanan, D. A. & Ernst, J. D. (1996). Phagosome-Lysosome Fusion Is a Calcium-independent Event in Macrophages. Journal of Cell Biology, 132(1-2), 49-61
Open this publication in new window or tab >>Phagosome-Lysosome Fusion Is a Calcium-independent Event in Macrophages
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1996 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 132, no 1-2, p. 49-61Article in journal (Refereed) Published
Abstract [en]

Phagosome-lysosome membrane fusion is a highly regulated event that is essential for intracellular killing of microorganisms, Functionally, it represents a form of polarized regulated secretion, which is classically dependent on increases in intracellular ionized calcium ([Ca2+](i)). Indeed, increases in [Ca2+](i) are essential for phagosome-granule (lysosome) fusion in neutrophils and for lysosomal fusion events that mediate host cell invasion by Trypanosoma cruzi trypomastigotes, Since several intracellular pathogens survive in macrophage phagosomes that do not fuse with lysosomes, we examined the regulation of phagosome-lysosome fusion in macrophages. Macrophages (MO) were treated with 12.5 mu M bis-(2-amino-S-methylphenoxy) ethane-N,N,N',N',-tetraacetic acid tetraacetoxymethyl ester (MAPT/AM), a cell-permeant calcium chelator which reduced resting cytoplasmic [Ca2+]; from 80 nM to less than or equal to 20 nM and completely blocked increases in [Ca2+](i) in response to multiple stimuli, even in the presence of extracellular calcium, Subsequently, MO phagocytosed serum-opsonized zymosan, staphylococci, or Mycobacterium bovis, Microbes were enumerated by 4',6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining, and phagosome-lysosome fusion was scored using both lysosome-associated membrane protein (LAMP-1) as a membrane marker and rhodamine dextran as a content marker for lysosomes, Confirmation of phagosomelysosome fusion by electron microscopy validated the fluorescence microscopy findings, We found that phagosome-lysosome fusion in MO occurs normally at very low [Ca2+](i) (less than or equal to 20 nM), Kinetic analysis showed that in MO none of the steps leading from particle binding to eventual phagosome-lysosome fusion are regulated by [Ca2+](i) in a rate-limiting way. Furthermore, confocal microscopy revealed no difference in the intensity of LAMP-1 immunofluorescence in phagolysosome membranes in calcium-buffered vs, control macrophages, We conclude that neither membrane recognition nor fusion events in the phagosomal pathway in macrophages are dependent on or regulated by calcium.

Place, publisher, year, edition, pages
Rockefeller University Press, 1996
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98037 (URN)10.1083/jcb.132.1.49 (DOI)A1996TR59300005 ()8567729 (PubMedID)
Available from: 2013-09-25 Created: 2013-09-25 Last updated: 2017-12-06Bibliographically approved
Majeed, M. (1994). Regulation of Attachment and Early Intracellular Development of Chlamydia trachomatis in Eucaryotic Cells. (Doctoral dissertation). Linköping: Linköpings universitet
Open this publication in new window or tab >>Regulation of Attachment and Early Intracellular Development of Chlamydia trachomatis in Eucaryotic Cells
1994 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The obligate intracellular bacterium, Chlamydia trachomatis , a common human pathogen, causing different diseases in both males and females, as well as in infants born to infected mothers. Occasionally, these diseases involve serious complications, such as blindness and infertility. C. trachomatis has a unique biphasic life cycle: after initial inclosure in membrane~bound endosomes, the infectious elementary bodies (EBs) reorganize to the metabolically actiVe forms (RBs); the RBs divide by binary fission, and after multiple divisions, they again differentiate to form new EBs, which are subsequently released from the host cell to start a new infectious cycle. As an attempt to investigate the early events of chlamydial infection, my results show that EBs bind with high affinity to collagen type I and heparan sulfate, suggesting that this selective affinity may mediate the attachment of chlamydiae to the surface of a host cell. ER-containing endosomes avoid fusion with host celllysosomes. However, within 30 min of form ation, these endosomes form one local aggregate in the central orperinuclear region of individual cells. This aggregation is reversible and time and temperature dependent, and requires viable EBs. Clathrin and F-actin are mobilized and colocalized with EB aggregates, suggesting that the aggregation of EBs is an active process that may be biologically involved in the infectivity of chlamydiae. The aggregation and inclusion formation of EBs, and the redistribution of F-actin seem to be controlled by both extra- and intracellular Ca2+, whereas the attachment and ingestion of EBs occur independently of Ca2+ in the growth medium and at low intracellular free Ca2+ [Ca2+]i. Moreover, chlamydiae do not induce any changes in the level of [Ca2+]i, this indicates that the aggregation of EBs requires a normal homeostasis of intracellular Ca2+. By affecting F-act:in reorganization and, putatively, certain Ca2+ -binding proteins, [Ca2+]i plays a vital role in the process of chlamydiae infection. The ca2+_ and phospholipid-binding proteins, annex.ins, are selectivelytranslocated during ehlamydial infection, i.e. annexins III, IV, and V, but not annexins I and VI, translocate to the proximity of chlamydial aggregates and inclusions. Annexins differ in their ability to associate with chlamydia-containing vesicles and inclusions. This fact implies that different factors regulate the interaction of annexins I and Ill with the membrane and also suggests that there is a selective regulatorymechanism that guides endosome aggregation and that is responsible for endosome avoiding lysosome fusion during chlamydial infection. Chlamydiae also induce mobilization of intracellular Ca2+ stores. This suggests that in a chlamydia-infected cell localized [Ca2+]i changes may occur by mobilization of Ca2+ stores at the sites of ca2+ action. The physiological role of ca2+ stores redistribution during infection of the host cells with chlamydiae might be to generate subceJlular [Ca2+]i gradients needed for the intracellular itinerary of the membrane trafficking of BE-containing endosomes.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 1994. p. 65
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 430
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28608 (URN)13763 (Local ID)91-7871-277-7 (ISBN)13763 (Archive number)13763 (OAI)
Public defence
1994-09-22, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Note
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-07-25Bibliographically approved
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