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

Abstract

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.

Targeted Deletion of Nrf2 Reduces Urethane-Induced Lung Tumor Development in Mice

“…At 9 wk, BAL cell clustering accompanied cytolysis, and this feature was markedly greater in Nrf2 -/- mice compared to Nrf2 +/+ mice (Figure S1). This observation is assumed to be associated with excess viscous secretion such as mucus as suggested by aggregation of cells with secreted mucus in Alcian Blue (pH 2.5)/periodic acid-Schiff (AB/PAS)-stained lungs (Figure S1), or by procoagulant activity due to fibrin deposition in mononuclear phagocytes which occurs during lung inflammation [16], [17]. Infiltrated neutrophils were obvious but not quantifiable due to extensive clustering and lysis of BAL cells in Nrf2 -/- mice; consistent with this observation, neutrophil myeloperoxidase (MPO) activity was significantly higher in Nrf2 -/- mice than in Nrf2 +/+ mice treated with urethane (Figure 1A).…”

Pulmonary tuberculosis induces a systemic hypercoagulable state

“…In accordance, a previous study also reported a trend towards enhanced procoagulant activity in BALF of patients with lung TB. 34 Taken together it is unlikely that local haemostatic alterations are the driving force behind the hypercoagulable state at the systemic level in patients with lung TB.…”

Role of Tissue Factor in Mycobacterium tuberculosis-Induced Inflammation and Disease Pathogenesis

“…Among other clinical presentations, increasing evidence indicates the presence of hematologic abnormalities, particularly disseminated intravascular coagulation (DIC) and deep-vein thrombosis (DVT), in TB patients [2] – [4] . The hemostatic and inflammatory changes in TB can result in a hypercoagulable state [3] , [5] . The prevalence of venous thromboembolism ranges from 0.6% to 3% in TB patients [6] and clinical reports emphasize that patients with severe pulmonary TB are at risk of developing thromboembolic events [7] .…”