Effect of Leukocytic Endogenous Mediator on Plasma Fibrinogen and Haptoglobin

Kampschmidt, Ralph F.; Upchurch, Herbert F.

doi:10.3181/00379727-146-38216

Cited by 52 publications

(20 citation statements)

References 5 publications

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“…We reasoned that these peptides must be influencing the hepatocyte through some indirect pathway. Studies from many laboratories (30)(31)(32)(33) as well as our own (15,27) kocyte could be a link in the pathway for fibrinogen synthesis that involves fragments D and E. When leukocytes were treated with fragment D or E they responded by producing a factor that when added to the isolated hepatocyte had a dramatic effect on fibrinogen synthesis. Neither fibrinogen nor fibrin stimulated leukocytes to product HSF; however, plasminolytic fragments D and E at the same molar concentration stimulated the production of HSF by the leukocytes.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

Ritchie¹,

Levy²,

Adams³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

103

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The effect of plasmin-derived fibrinogen fragments on the biosynthesis of fibrinogen was investigated in cultured monolayers ofrat hepatocytes. Incubating the cells with several concentrations of either fibrinogen or fibrin fragment D or E had no effect on the synthesis and secretion of fibrinogen by these cells. However, if the fragments were incubated with isolated peripheral blood leukocytes, they caused these cells to secrete a factor that when added to the hepatocytes caused an increase in fibrinogen synthesis 4-to 6-fold over controls. Moreover, the hepatocyte-stimulating factor also affected the production of several other proteins produced by the hepatocyte. These results demonstrate that both fragments D and E can stimulate hepatic fibrinogen synthesis via an indirect leukocyte-mediated pathway.When fibrinogen or fibrin is acted upon by plasmin, a series of well-defined proteolytic cleavages occur that ultimately result in the formation of two different molecular species that come from different parts of the molecule. The fragments are designated E, which is derived from the amino-terminal region of the molecule and has a Mr of 40,000, and D, which is derived from the carboxy-terminal region and has a Mr of 80,000 (1, 2). Slightly more than a decade ago, Barnhardt et al (3) infused fibrinolytic fragments into dogs and found a significant increase in fibrinogen synthesis as judged by an increased immunofluorescence of liver slices taken several hours after the infusion. The observation that some of the plasminolytic fragments derived from fibrinogen or fibrin maybe involved in the regulation of fibrinogen synthesis was suggestive of a novel regulatory pathway that could be an important part of the inflammatory response.A number of reports has appeared (4-8) which seem to verify and expand the study of Barnhardt et al.-that is, they suggest that either fibrinogen degradation products or fibrin degradation products (FDP or fdp, respectively) play an important role in regulating fibrinogen synthesis. On the other hand, several other studies (9)(10)(11)(12) have been unable to demonstrate any effects of FDP on fibrinogen production. Unfortunately there is no consistent explanation for these conflicting observations. Thus, whether FDP play any significant role in regulating fi--brinogen is still unresolved.In this report we have characterized a role that FDP play in regulating fibrinogen synthesis by exposing cultured hepatocytes to purified fragments offibrinogen and fibrin. We provide evidence that the fragments, do not stimulate fibrinogen synthesis by direct interaction with the hepatocyte. However, the fragments do affect fibrinogen synthesis by stimulating leukocytes to produce a potent hepatocyte-stimulating factor (HSF), which then acts on the hepatocytes to increase fibrinogen synthesis. We also demonstrate that both fragments are equally potent in causing the production of HSF. These results show the pathway by which FDP stimulate fibrinogen production. MATERIALS AND METHODSPreparation of R...

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Section: Discussionmentioning

confidence: 91%

“…2 (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). The protein fraction from rabbit leukocytes that contains these biological activities has collectively beemr termed leukocyte endogenous mediator, or LEM (34).…”

Section: Resultsmentioning

confidence: 99%

Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

Ritchie¹,

Levy²,

Adams³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

103

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“…Since the in crease in serum Hp tends to be correlated with the severity of the inflammatory stimulus or condition [12,14,15], it has been suggested that Hp levels may serve as an indicator of the activity of cells of the reticuloendothelial system [11,12]. Thus, in the absence of hemolytic or non-malignant inflamma tory conditions, the Hp response to a tumor may be a reflec tion of its inflammatory characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies indicate that Hp elevation is mediated by factors released into the circulation from macrophages [11,12] or granulocytes [14] at the site of inflammation. Since the in crease in serum Hp tends to be correlated with the severity of the inflammatory stimulus or condition [12,14,15], it has been suggested that Hp levels may serve as an indicator of the activity of cells of the reticuloendothelial system [11,12].…”

Section: Discussionmentioning

confidence: 99%

Serum Haptoglobin Levels in Mice with 7,12-Dimethylbenz[a]anthracene-induced Tumors

Palmer¹,

Ulland²

1978

Oncology

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Serum haptoglobin (Hp) levels were determined periodically in mice treated with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The magnitude and duration of the Hp response to tumors induced by DMBA were dependent on the tumor type; lymphocytic lymphomas elicited a minimal response, whereas mice bearing mammary carcinomas and stomach squamous cell carcinomas had high Hp levels which remained elevated throughout most of the period of tumor development. In the majority of mice with mammary carcinomas, the initial rise in serum Hp coincided fairly closely with the first appearance of palpable masses. Some variation in the magnitude ot the Hp response was observed between individual mice bearing chemically-induced tumors of similar histological types.

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“…4 This mediator was later purified, defined as a cytokine and named interleukin-1. Subsequently, a number of cytokines involved in inducing changes in liver synthesis have been identified, purified and cloned.…”

Section: Introductionmentioning

confidence: 99%

In vivo changes in plasma acute phase protein levels in the rat induced by slow release of IL‐1, IL‐6 and TNF

Lewis

Sedgwick

Hanahoe

1992

Mediators of Inflammation

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ADMINISTRATION of large doses of cytokines by injection is required to induce changes in acute phase protein levels.Comparisons were made in the rat of the effects of administering recombinant human cytokines by injection with continuous release from implanted osmotic minipumps.Continuous release of interleukin-lfl (0.2-2.1 ng h -1) induced dose-related changes in the plasma levels of albumin, seromucoid proteins, haptoglobin and caeruloplasmin; interleukin-10 had similar effects but required higher doses (2-21 ng h-l). Tumour necrosis factor (50 ng h -1) only significantly increased seromucoid levels, whereas IL-6 (3-30 ng h -1) induced haptoglobin and caeruloplassynthesis. This method provides a better technique for studying the in rive effects of cytokines which may be relevant to the release mechanisms in inflammation.

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Effect of Leukocytic Endogenous Mediator on Plasma Fibrinogen and Haptoglobin

Cited by 52 publications

References 5 publications

Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

Serum Haptoglobin Levels in Mice with 7,12-Dimethylbenz[a]anthracene-induced Tumors

In vivo changes in plasma acute phase protein levels in the rat induced by slow release of IL‐1, IL‐6 and TNF

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