Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease.

Chapman, Harold A.; Allen, Cheryl; Stone, O L; Fair, Daryl S.

doi:10.1172/jci111922

Cited by 95 publications

(51 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44). It was previously reported that TF is absent in the normal lung, but is highly expressed by hyperplastic epithelial cells overlying fibrotic foci in patients with fibrotic lung disease (14), whereas FVII has previously been shown to be expressed and upregulated by alveolar macrophages isolated from patients with sarcoidosis (45). The present report shows that TF, FVII, and FX colocalize to the epithelium overlying fibrotic foci in IPF, so that FX is likely to be present at sites where it can be activated in the TF/FVIIa/FXa ternary complex.…”

Section: Discussionmentioning

confidence: 98%

Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury

Scotton¹,

Krupiczojc²,

Königshoff³

et al. 2009

J. Clin. Invest.

206

245

View full text Add to dashboard Cite

Uncontrolled activation of the coagulation cascade contributes to the pathophysiology of several conditions, including acute and chronic lung diseases. Coagulation zymogens are considered to be largely derived from the circulation and locally activated in response to tissue injury and microvascular leak. Here we report that expression of coagulation factor X (FX) is locally increased in human and murine fibrotic lung tissue, with marked immunostaining associated with bronchial and alveolar epithelia. FXa was a potent inducer of the myofibroblast differentiation program in cultured primary human adult lung fibroblasts via TGF-β activation that was mediated by proteinase-activated receptor-1 (PAR1) and integrin α v β 5 . PAR1, α v β 5 , and α-SMA colocalized to fibrotic foci in lung biopsy specimens from individuals with idiopathic pulmonary fibrosis. Moreover, we demonstrated a causal link between FXa and fibrosis development by showing that a direct FXa inhibitor attenuated bleomycin-induced pulmonary fibrosis in mice. These data support what we believe to be a novel pathogenetic mechanism by which FXa, a central proteinase of the coagulation cascade, is locally expressed and drives the fibrotic response to lung injury. These findings herald a shift in our understanding of the origins of excessive procoagulant activity and place PAR1 central to the cross-talk between local procoagulant signaling and tissue remodeling.

show abstract

Section: Discussionmentioning

confidence: 98%

Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury

Scotton¹,

Krupiczojc²,

Königshoff³

et al. 2009

J. Clin. Invest.

206

245

View full text Add to dashboard Cite

show abstract

“…In previous studies, procoagulant activity attributable to components of the extrinsic coagulation pathway has been described in the alveolar compartment of man and experimental animals (2,19,21,23,(43)(44)(45)(46)(47)(48). In addition, fibrinolytic activity attributable to urokinase or urokinase-like PA has been described in BAL and macrophages from the lower respiratory tract of humans and animals (23,41,49,50).…”

Section: Discussionmentioning

confidence: 97%

“…In addition, fibrinolytic activity attributable to urokinase or urokinase-like PA has been described in BAL and macrophages from the lower respiratory tract of humans and animals (23,41,49,50). Under normal circumstances, little procoagulant activity (21,47,48) and relatively high levels of fibrinolytic activity (23, tologic hallmark of ARDS (3), and can be a prominent feature of the ILD and pneumonitides (1, 2). These observations suggest that the normal homeostasis of coagulation and fibrinolytic processes is disturbed in human lung injury and that conditions that promote fibrin deposition are established in the alveolar compartment.…”

Section: Discussionmentioning

confidence: 99%

Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.

Idell¹,

James²,

Levin³

et al. 1989

J. Clin. Invest.

Self Cite

329

231

View full text Add to dashboard Cite

To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P < 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to a2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.

show abstract

“…Bronchoalveolar lavage fluids and lung alveolar macrophages from humans have been shown to contain procoagulant activities [25][26][27][28][29]. Furthermore, it has been shown that the PCA of the lavage fluids are membrane vesicles consisting exclusively of alveolar macrophage membrane material [25,29,30].…”

Section: Discussionmentioning

confidence: 99%

Procoagulant activity of bronchoalveolar lavage fluids taken from the site of tuberculous lesions

Selvaraj

Venkataprasad²,

Vk³

et al. 1994

Eur Respir J

View full text Add to dashboard Cite

P Pr ro oc co oa ag gu ul la an nt t a ac ct ti iv vi it ty y o of f b br ro on nc ch ho oa al lv ve eo ol la ar r l la av va ag ge e f fl lu ui id ds s t ta ak ke en n f fr ro om m t th he e s si it te e o of f t tu ub be er rc cu ul lo ou us s l le es si io on ns s ABSTRACT: We wanted to determine the procoagulant activity (PCA) of bronchoalveolar lavage fluids, in order to understand the macrophage-mediated lung injury at the site of tuberculous lesion. Alveolar lavage fluids taken from the site of a lesion (radiologically abnormal site (RAS)) and an unaffected site (radiologically normal site (RNS)) of active pulmonary tuberculosis (TB) patients (n=7) and inactive (cured) patients (n=9) were studied for their PCA producing potential. The observed results were not significant using Mann-Whitney test, and thus all increases/decreases reported below are trends/ tendancies only.An increased PCA was seen in 4 out of 7 cell-free lavage supernatants of active-TB taken from the site of lesion (RAS), compared to only 1 out of 9 in inactive-TB. The PCA producing potential of the alveolar macrophages of RAS and RNS of active-TB patients was enhanced when the alveolar macrophages were cocultured with autologous peripheral blood lymphocytes under in vitro condition. Stimulation with purified protein derivative (PPD) of M. tuberculosis showed a variable (increased or decreased) PCA production. Peripheral blood monocytes and total mononuclear cells (monocytes + lymphocytes) of active-TB patients stimulated with or without PPD showed increased PCA production, compared with normal individuals and inactive-TB patients.The present study suggests that increased production of PCA by the alveolar macrophages, in collaboration with lymphocytes and other cells at the site of tuberculous lesions will result in fibrin formation. The deposition of fibrin in the alveoli may lead to further lung injury.

show abstract

Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease.

Cited by 95 publications

References 38 publications

Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury

Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury

Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.

Procoagulant activity of bronchoalveolar lavage fluids taken from the site of tuberculous lesions

Contact Info

Product

Resources

About