Phagocytosis of Escherichia coli by Insect Hemocytes Requires Both Activation of the Ras/Mitogen-activated Protein Kinase Signal Transduction Pathway for Attachment and β3 Integrin for Internalization

Foukas, Lazaros C.; Katsoulas, Haralabos L.; Paraskevopoulou, Nikolitsa; Metheniti, Aristea; Lambropoulou, María; Marmaras, Vassilis J.

doi:10.1074/jbc.273.24.14813

Cited by 96 publications

(71 citation statements)

References 29 publications

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“…It has been shown that integrin receptors can be internalized after binding either endogenous ligands (eg, ␣IIb␤3 binding of fibrinogen 32 ) or exogenous ligands (eg, bacteria 33,34 ), and the ␣2␤1 receptor on platelets has also been shown to internalize collagen fragments ex vivo. 21 However, a role for integrin receptor internalization in vivo as a mechanism for dynamically regulating the adhesion of hematopoietic cells that need to migrate extensively has not been previously explored.…”

Section: Discussionmentioning

confidence: 99%

Negative regulation of activated α2 integrins during thrombopoiesis

Zou

Schmaier

Cheng

et al. 2009

Blood

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Circulating platelets exhibit rapid signaling and adhesive responses to collagen that facilitate hemostasis at sites of vessel injury. Because platelets are anuclear, their collagen receptors must be expressed by megakaryocytes, platelet precursors that arise in the collagen-rich environment of the bone marrow. Whether and how megakaryocytes regulate collagen adhesion during their development in the bone marrow are unknown. We find that surface expression of activated, but not wild-type, ␣2 integrins in hematopoietic cells in vivo results in the generation of platelets that lack surface ␣2 receptors. Culture of hematopoietic progenitor cells ex vivo reveals that surface levels of activated, but not wild-type, ␣2 integrin receptors are rapidly down-regulated during cell growth on collagen but reach wild-type levels when cells are grown in the absence of collagen. Progenitor cells that express activated ␣2 integrins are normally distributed in the bone marrow in vivo and exhibit normal migration across a collagen-coated membrane ex vivo. This migration is accompanied by rapid down-regulation of activated surface integrins. These studies identify ligand-dependent removal of activated ␣2 receptors from the cell surface as a mechanism by which integrin function can be negatively regulated in hematopoi IntroductionHematopoietic cells develop as adherent cells in contact with matrix proteins in the bone marrow until they are released as nonadherent cells into the circulating blood. Circulating platelets use collagen receptors to mediate platelet activation and firm adhesion in response to exposed vessel wall collagen as a primary hemostatic response. 1,2 A critical platelet adhesive receptor for collagen that is expressed by mature megakaryocytes and platelets is integrin ␣2␤1. Like other platelet integrins, ␣2␤1 is held in a low-affinity conformation and unable to bind ligand until activating receptors on the platelet surface generate the "inside-out" intracellular signals that allosterically expose the ligand-binding ␣2 I domain. 3,4 Platelet activation signals are generated either by soluble ligands such as thrombin or ADP or by the glycoprotein VI (GPVI) receptor, an immune receptor homolog that activates platelets directly in response to collagen. [5][6][7] Affinity modulation of integrins is mediated by the interaction of talin with the integrin ␤ subunit and subsequent induction of a conformational change in the ␣ subunit from a low-to a high-affinity state. Once activated, integrin ␣2␤1 mediates firm adhesion of circulating platelets to exposed vessel wall matrix and provides a foundation for platelet thrombus formation at sites of vessel injury. [8][9][10] An outstanding question regarding platelet collagen responses is how platelets can be programmed to rapidly respond to minute amounts of collagen yet arise from megakaryocytes in the collagen-rich environment of the bone marrow. Megakaryocyte maturation is thought to require migration within the bone marrow from the osteoblastic stem cell niche to the bone ...

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Section: Discussionmentioning

confidence: 99%

Negative regulation of activated α2 integrins during thrombopoiesis

Zou

Schmaier

Cheng

et al. 2009

Blood

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“…Certainly there are others, and recent work with LPS is beginning to reveal some of them. Foukas et al (1998) suggested that the Ras/mitogen-activated protein kinase pathway and integrin receptors are required for cellular internalization of LPS by hemocytes from C. capitata. So far, then, eicosanoids, biogenic amines and kinase pathways have been recognized as important elements in mediating cellular defense reactions to bacterial challenge.…”

Section: Discussionmentioning

confidence: 99%

Insect cellular reactions to the lipopolysaccharide component of the bacterium Serratia marcescens are mediated by eicosanoids

Bedick

Pardy

Howard³

et al. 2000

Journal of Insect Physiology

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Nodulation, which begins with the formation of cellular microaggregates, is the predominant cellular defense reaction to bacterial infections in insects. We suggested that these reactions to bacterial infections are mediated by eicosanoids. The lipopolysaccharide (LPS) component of some bacterial cells stimulates defense reactions in mammals and insects. Here, we report on experiments designed to test the hypothesis that eicosanoids mediate microaggregation reactions to LPS. Injections of LPS (purified from the bacterium, Serratia marcescens) into larvae of the tenebrionid beetle, Zophobas atratus, stimulated microaggregation reactions in a dose-dependent manner. Treatments with eicosanoid-biosynthesis inhibitors immediately prior to LPS challenge sharply reduced the microaggregation responses. Separate treatments with specific inhibitors of phospholipase A 2 , cyclooxygenase and lipoxygenase reduced microaggregation, supporting our view that microaggregate formation involves lipoxygenase and cyclooxygenase products. The inhibitory influence of dexamethasone was apparent within 30 min after injection, and microaggregation was significantly reduced, relative to control insects, over the following 90 min. The dexamethasone effects were reversed by treating LPS-injected insects with the eicosanoid precursor, arachidonic acid. These findings indicate that cellular defense reactions to a specific component of bacterial cells are mediated by eicosanoids, and open up new possibilities for dissecting detailed hemocytic actions in insect immune reactions to bacterial infections.

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“…The defense system of invertebrates is based on both cellular and humoral immune responses (6). The former includes encapsulation (7)(8)(9), phagocytosis (10), and nodule formation (11). The clotting system of arthropods (12,13), the synthesis of a broad spectrum of potent antimicrobial proteins in many insects (14,15) and crustaceans (16 -18), and the prophenoloxidase activating system (proPO system) (2) belong to the last immune response.…”

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confidence: 99%

A Lipopolysaccharide- and β-1,3-Glucan-binding Protein from Hemocytes of the Freshwater Crayfish Pacifastacus leniusculus

Lee

Wang

Söderhäll

2000

Journal of Biological Chemistry

273

159

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A lipopolysaccharide-and ␤-1,3-glucan-binding protein (LGBP) was isolated and characterized from blood cells (hemocytes) of the freshwater crayfish Pacifastacus leniusculus. The LGBP was purified by chromatography on Blue-Sepharose and phenyl-Sepharose, followed by Sephacryl S-200. The LGBP has a molecular mass of 36 kDa and 40 kDa on 10% SDS-polyacrylamide gel electrophoresis under reducing and nonreducing conditions, respectively. The calculated mass of LGBP is 39,492 Da, which corresponds to the native size of LGBP; the estimated pI of the mature LGBP is 5.80. LGBP has binding activity to lipopolysaccharides as well as to ␤-1,3-glucans such as laminarin and curdlan, but peptidoglycan could not bind to LGBP. Cloning and sequencing of LGBP showed significant homology with several putative Gram-negative bacteria-binding proteins and ␤-1,3-glucanases. Interestingly, LGBP also has a structure and functions similar to those of the coelomic cytolytic factor-1, a lipopolysaccharide-and glucan-binding protein from the earthworm Eisenia foetida. To evaluate the involvement of LGBP in the prophenoloxidase (proPO) activating system, a polyclonal antibody against LGBP was made and used for the inhibition of phenoloxidase (PO) activity triggered by the ␤-1,3-glucan laminarin in the hemocyte lysate of crayfish. The PO activity was blocked completely by the anti-LGBP antibody. Moreover, the PO activity could be recovered by the addition of purified LGBP. These results suggest that the 36-kDa LGBP plays a role in the activation of the proPO activating system in crayfish and thus seems to play an important role in the innate immune system of crayfish.Vertebrates and invertebrates are capable of initiating several kinds of defense mechanisms after recognition of bacterial and fungal cell wall molecules, such as lipopolysaccharides (LPS), 1 peptidoglycans, and ␤-1,3-glucans (1-3). In the case of humans, monocytes and macrophages respond to LPS by inducing the expression of cytokines, cell adhesion proteins, and enzymes involved in the production of small proinflammatory mediators. Under pathophysiological conditions, LPS exposure can lead to an often fatal syndrome known as septic shock (4).Invertebrate animals lack antibodies and hence an adaptive immune response, and instead they have efficient innate immune systems to defend themselves against invading foreign materials (5). The defense system of invertebrates is based on both cellular and humoral immune responses (6). The former includes encapsulation (7-9), phagocytosis (10), and nodule formation (11). The clotting system of arthropods (12, 13), the synthesis of a broad spectrum of potent antimicrobial proteins in many insects (14, 15) and crustaceans (16 -18), and the prophenoloxidase activating system (proPO system) (2) belong to the last immune response. Moreover, the humoral immune response is also triggered by LPS or ␤-1,3-glucans (2, 19) as in vertebrates. Therefore, the proteins involved in the recognition of LPS, peptidoglycans, and ␤-1,3-glucans have been named pa...

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Phagocytosis of Escherichia coli by Insect Hemocytes Requires Both Activation of the Ras/Mitogen-activated Protein Kinase Signal Transduction Pathway for Attachment and β3 Integrin for Internalization

Cited by 96 publications

References 29 publications

Negative regulation of activated α2 integrins during thrombopoiesis

Negative regulation of activated α2 integrins during thrombopoiesis

Insect cellular reactions to the lipopolysaccharide component of the bacterium Serratia marcescens are mediated by eicosanoids

A Lipopolysaccharide- and β-1,3-Glucan-binding Protein from Hemocytes of the Freshwater Crayfish Pacifastacus leniusculus

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