TNF-α stimulates the biosynthesis of complement C3 and factor B by human umbilical cord vein endothelial cells

Kawakami, Yasuhiko; Watanabe, Yoshiki; Yamaguchi, M; Sakaguchi, Haruko; Kono, Ichiro; Ueki, Ayako

doi:10.1016/s0304-3835(97)04737-x

Cited by 30 publications

(23 citation statements)

References 17 publications

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“…If this is the case, then the chemotactic factor C5a could be implicated. It has been shown previously that chlamydial EB could activate the alternative complement pathway (13), but stimulation of the biosynthesis of C3 by TNF-␣ has also been demonstrated (10). It is important to note that at this early stage after inoculation that UV-inactivated organisms did not elicit a chemokine or cytokine response, even though it was probable that there was free LPS or other products in the inoculum which one might suspect to be capable of eliciting a response.…”

Section: Discussionmentioning

confidence: 81%

Host Chemokine and Cytokine Response in the Endocervix within the First Developmental Cycle of Chlamydia muridarum

Rank¹,

Lacy²,

Goodwin

et al. 2010

Infect Immun

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The initial host response in a primary chlamydial infection is the onset of acute inflammation. However, we still know very little about the early temporal events in the induction of the acute inflammatory response and how these events relate to the initial chlamydial developmental cycle in an actual genital infection. Because it was critical to initiate a synchronous infection in the endocervix in the first 24 h to evaluate the sequential expression of the host response, we developed the surgical methodology of depositing Chlamydia muridarum directly on the endocervix. Cervical tissue was collected at 3, 12, and 24 h after inoculation and the expression array of chemokines, cytokines, and receptors was assessed to characterize the response during the initial developmental cycle. Polymorphonuclear leukocyte (PMN) infiltration was first observed at 12 h after inoculation, and a few PMNs could be seen in the epithelium at 24 h. Electron microscopic analysis at 24 h showed that virtually all inclusions were at the same stage of development, indicating a synchronous infection. Several chemokine and cytokine genes were expressed as early as 3 h after infection, but by 12 h, 41 genes were expressed. Thus, activation of the host response occurs both with the introduction of elementary bodies into the host and early replication of reticulate bodies. No significant response was observed when UV-inactivated organisms were inoculated into the cervix at any time interval. This model provides an ideal opportunity to investigate the mechanisms by which the early inflammatory response is induced in vivo.

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Section: Discussionmentioning

confidence: 81%

Host Chemokine and Cytokine Response in the Endocervix within the First Developmental Cycle of Chlamydia muridarum

Rank¹,

Lacy²,

Goodwin

et al. 2010

Infect Immun

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“…Both control and experimental flasks were incubated in serum-free media for a total of 24 h to eliminate any proteins derived from serum that might affect surface receptor detection. The specific concentrations and duration of exposure of TNF and IL-1b were chosen based on use of these cytokines in EC gene expression studies (40)(41)(42). Cell surface labeling of CD55, CD46, CD59, and CD141.…”

Section: Flow Cytometrymentioning

confidence: 99%

TNF Regulates Essential Alternative Complement Pathway Components and Impairs Activation of Protein C in Human Glomerular Endothelial Cells

Sartain

Turner

Moake

2016

The Journal of Immunology

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Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe renal injury secondary to an overactive alternative complement pathway (AP). aHUS episodes are often initiated or recur during inflammation. We investigated gene expression of the surface complement regulatory proteins (CD55, CD59, CD46, and CD141 [thrombomodulin]) and AP components in human glomerular microvascular endothelial cells (GMVECs) and in HUVECs, a frequently used investigational model of endothelial cells. Surface complement regulatory proteins were also quantified by flow cytometry. All experiments were done with and without exposure to IL-1β or TNF. Without cytokine stimulation, we found that GMVECs had greater AP activation than did HUVECs. With TNF stimulation, THBD gene expression and corresponding CD141 surface presence in HUVECs and GMVECs were reduced, and gene expression of complement components C3 (C3) and factor B (CFB) was increased. Consequently, AP activation, measured by Ba production, was increased, and conversion of protein C (PC) to activated PC by CD141-bound thrombin was decreased, in GMVECs and HUVECs exposed to TNF. IL-1β had similar, albeit lesser, effects on HUVEC gene expression, and it only slightly affected GMVEC gene expression. To our knowledge, this is the first detailed study of the expression/display of AP components and surface regulatory proteins in GMVECs with and without cytokine stimulation. In aHUS patients with an underlying overactive AP, additional stimulation of the AP and inhibition of activated PC–mediated anticoagulation in GMVECs by the inflammatory cytokine TNF are likely to provoke episodes of renal failure.

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“…Moreover, our crosscomplementation experiments demonstrated that elastase specifically in Activation of the alternative complement pathway occurs continuously in vivo through the C3 ''tick-over'' pathway. LPS, the ''preparative agent'' in the Shwartzman reaction, significantly increases C3 synthesis (Colten et al, 1986;Thorbecke et al, 1965), and TNF promotes synthesis and release of complement components C3 and factor B by endothelial cells, thus leading to further opportunities for local activation of complement (Kawakami et al, 1997). TNF promotes endothelial cell retraction, with subsequent exposure of the subendothelial extracellular matrix (ECM), which is a target for C3b/iC3b fixation (Hindmarsh and Marks, 1998).…”

Section: Figure 6 Adhesion Of Neutrophils To Complement-coated Surfacesmentioning

confidence: 99%

Mac-1 Signaling via Src-Family and Syk Kinases Results in Elastase-Dependent Thrombohemorrhagic Vasculopathy

et al. 2006

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CD18 integrins promote neutrophil recruitment, and their engagement activates tyrosine kinases, leading to neutrophil activation. However, the significance of integrin-dependent leukocyte activation in vivo has been difficult to prove. Here, in a model of thrombohemorrhagic vasculitis, the CD18 integrin Mac-1 on neutrophils recognized complement C3 deposited within vessel walls and triggered a signaling pathway involving the Src-family kinase Hck and the Syk tyrosine kinase. This led to neutrophil elastase release, causing hemorrhage, fibrin deposition, and thrombosis. Mice genetically deficient in any of these components (C3, Mac-1, Hck, Syk, or elastase) were resistant to disease despite normal tissue neutrophil accumulation. Disease was restored in Mac-1-deficient mice infused with wild-type, but not kinase- or elastase-deficient, neutrophils. Elastase release in the inflamed tissue was reduced in Mac-1-deficient mice, and a deficiency of Mac-1 or the kinases blocked neutrophil elastase release in vitro. These data suggest that Mac-1 engagement of complement activates tyrosine kinases to promote elastase-dependent blood vessel injury in vivo.

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TNF-α stimulates the biosynthesis of complement C3 and factor B by human umbilical cord vein endothelial cells

Cited by 30 publications

References 17 publications

Host Chemokine and Cytokine Response in the Endocervix within the First Developmental Cycle of Chlamydia muridarum

Host Chemokine and Cytokine Response in the Endocervix within the First Developmental Cycle of Chlamydia muridarum

TNF Regulates Essential Alternative Complement Pathway Components and Impairs Activation of Protein C in Human Glomerular Endothelial Cells

Mac-1 Signaling via Src-Family and Syk Kinases Results in Elastase-Dependent Thrombohemorrhagic Vasculopathy

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