Role of the Clotting System in Cell-Mediated Hypersensitivity

Colvin, Robert B.; Johnson, Richard A.; Mihm, Martín C.; Dvorak, Harold F.

doi:10.1084/jem.138.3.686

Cited by 182 publications

(60 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was demonstrated that fibrinogen and fibrin contribute to inflammation by inducing leukocyte migration (22)(23)(24). Later, in vitro and in vivo studies demonstrated that fibrin(ogen) alters inflammation not only by affecting leukocyte migration, but also by directly modulating the inflammatory response of leukocytes and ECs via an increased cytokine/chemokine response.…”

Section: Inflammatory Potential Of Fibrinogen and Fibrinmentioning

confidence: 99%

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Jennewein

Tran

Paulus

et al. 2011

Mol Med

206

139

View full text Add to dashboard Cite

Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as arthritis, multiple sclerosis or sepsis, an uncontrolled activation of the coagulation system contributes to inflammation, microvascular failure and organ dysfunction. Coagulation is initiated by the activation of thrombin, which, in turn, triggers fibrin formation by the release of fibrinopeptides. Fibrin is cleaved by plasmin, resulting in clot lysis and an accompanied generation of fibrin fragments such as D and E fragments. Various coagulation factors, including fibrinogen and/or fibrin [fibrin(ogen)] and also fibrin degradation products, modulate the inflammatory response by affecting leukocyte migration and cytokine production. Fibrin fragments are mostly proinflammatory, however, Bβ15-42 in particular possesses potential antiinflammatory effects. Bβ15-42 inhibits Rho-kinase activation by dissociating Fyn from Rho and, hence prevents stress-induced loss of endothelial barrier function and also leukocyte migration. This article summarizes the state-of-the-art in inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role fibrin fragments play during inflammation and, possibly, disease development.

show abstract

Section: Inflammatory Potential Of Fibrinogen and Fibrinmentioning

confidence: 99%

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Jennewein

Tran

Paulus

et al. 2011

Mol Med

206

139

View full text Add to dashboard Cite

show abstract

“…We have looked, therefore, for the deposition of Ig and C3 in vessels, or other parts of freshly grafted skin, during the period when it is insensitive to MARS. Anti-graft serum, either MARS or RARS that had been absorbed with mouse tissues, was injected intraperitoneally at a dose of 0.5 ml, and the grafts were removed 2-4 h later and prepared for examination with fluoresceinated antisera as described elsewhere (6). Rabbit antiserum was used in some experiments because it was thought to facilitate the distinction between endogenous and injected immunoglobulins in this experimental system.…”

Section: Influence Of Surgical Dressings and The Regimen Of Lmmunosupmentioning

confidence: 99%

“…Grafts were excised from their hosts and cryostat sections of them were prepared for studies with fluorescent antisera as described previously (6). Fluoresceinconjugated antibodies reactive with rabbit IgG, mouse IgG, mouse C3, chicken IgG, or mouse serum albumin were obtained from N. L. Cappel Laboratories (Cochranville, Pa.).…”

mentioning

confidence: 99%

The vascular bed as the primary target in the destruction of skin grafts by antiserum. I. Resistance of freshly placed xenografts of skin to antiserum

Jooste¹,

Colvin²,

Soper³

et al. 1981

The Journal of Experimental Medicine

View full text Add to dashboard Cite

We have shown that both xenografts and allografts of rat skin can be acutely and severely damaged by antisera specifically reactive with graft antigens, and that in appropriate circumstances the phenomenon can be elicited routinely (1, 2). A matter of paramount importance among the variables that influence the occurrence of this form of immunologically mediated tissue damage is the interval of time between the placement of the grafts and the administration of antiserum (3). Contrary to widely held views on the special vulnerability of grafts that are healing into place, it has been found that antiserum injected at the time of grafting or within 5-6 d thereafter has little detectable influence on the course or time of survival of the transplanted skin. This period of insusceptibility is rapidly succeeded by a state of sensitivity to humoral antibody that, in immunosuppressed hosts, reaches a peak of intensity at about 14-16 d after grafting and persists at decreasing levels for an additional 3 wk. Grafts that survive beyond that period of time regain their resistance to antiserum, and this state is maintained for the duration of survival of the grafts.We have analyzed these changes in the responses of xenografts of skin to antisera, and we have found that the initial state of insensitivity differs substantively from that observed in long-standing grafts. We describe here the results of our studies on freshly placed grafts, and in a succeeding paper (4) we report on the mechanisms involved in the acquired resistance of grafts that have survived for relatively long periods of time. Materials and MethodsAnimals. B6AF1 and CAFa mice were purchased from The Jackson Laboratory, Bar Harbor, Maine. Lewis (LE) and (Le × BN)F1 hybrid rats (LBN) were obtained from Microbiological Associates, Walkersville, Md. CD rats were purchased from the Charles River Breeding Laboratories, Wilmington, Mass.Antisera. Rabbit anti-mouse thymocyte serum (RAMTS) 1 was prepared as described (5) or was obtained from Microbiological Associates. 13 pools of antisera were used, the least potent of which extended the mean survival time of rat skin grafts to 32.5 :t: ! 1 d. Rabbit anti-rat *

show abstract

“…Accordingly, injury, infection, and (auto)immunity are associated with extravascular fibrin(ogen) (3)(4)(5)(6).…”

mentioning

confidence: 99%

Fibrinogen Stimulates Macrophage Chemokine Secretion Through Toll-Like Receptor 4

Smiley

King

Hancock

2001

The Journal of Immunology

869

583

View full text Add to dashboard Cite

Extravascular fibrin deposition is an early and persistent hallmark of inflammatory responses. Fibrin is generated from plasma-derived fibrinogen, which escapes the vasculature in response to endothelial cell retraction at sites of inflammation. Our ongoing efforts to define the physiologic functions of extravasated fibrin(ogen) have led to the discovery, reported here, that fibrinogen stimulates macrophage chemokine secretion. Differential mRNA expression analysis and RNase protection assays revealed that macrophage inflammatory protein-1α (MIP-1α), MIP-1β, MIP-2, and monocyte chemoattractant protein-1 are fibrinogen inducible in the RAW264.7 mouse macrophage-like cell line, and ELISA confirmed that both RAW264.7 cells and primary murine thioglycolate-elicited peritoneal macrophages up-regulate the secretion of monocyte chemoattractant protein-1 >100-fold upon exposure to fibrinogen. Human U937 and THP-1 precursor-1 (THP-1) monocytic cell lines also secreted chemokines in response to fibrinogen, upon activation with IFN-γ and differentiation with vitamin D3, respectively. LPS contamination could not account for our observations, as fibrinogen-induced chemokine secretion was sensitive to heat denaturation and was unaffected by the pharmacologic LPS antagonist polymyxin B. Nevertheless, fibrinogen- and LPS-induced chemokine secretion both apparently required expression of functional Toll-like receptor 4, as each was diminished in macrophages derived from C3H/HeJ mice. Thus, innate responses to fibrinogen and bacterial endotoxin may converge at the evolutionarily conserved Toll-like recognition molecules. Our data suggest that extravascular fibrin(ogen) induces macrophage chemokine expression, thereby promoting immune surveillance at sites of inflammation.

show abstract

Role of the Clotting System in Cell-Mediated Hypersensitivity

Cited by 182 publications

References 23 publications

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

The vascular bed as the primary target in the destruction of skin grafts by antiserum. I. Resistance of freshly placed xenografts of skin to antiserum

Fibrinogen Stimulates Macrophage Chemokine Secretion Through Toll-Like Receptor 4

Contact Info

Product

Resources

About