Tissue factor in bronchoalveolar lavage fluids. Evidence for an alveolar macrophage source

Abstract

Local and systemic coagulation and fibrin deposition occur in many types of alveolar injury and inflammation, but clotting factors capable of initiating the coagulation cascade in the alveolus have not been thoroughly identified and characterized. In the present studies, BAL (bronchoalveolar lavage) fluids obtained from rabbits were found to have procoagulant activity detectable in dilutions containing as little as 1.3 ng of protein. The specific activity of the procoagulant in these fluids was within 1 order of magnitude of that found in brain thromboplastin. The BAL procoagulant was shown to be associated with particles having a molecular weight greater than 15 X 10(6) daltons by gel filtration chromatography, and was characterized as tissue factor by showing specific requirements for factors VII, X, and II. Further experiments were performed using membranes purified from alveolar macrophages by sucrose density gradients and characterized by studies of alkaline phosphodiesterase I, a cytoplasmic membrane marker, and electron microscopy. These studies demonstrate that alveolar macrophages, especially low-density subpopulations, generate and release membrane material that is a source of tissue factor in BAL fluids.