Expression of leukocyte integrins and tissue factor in mononuclear phagocytes

Abstract

The development of adult respiratory distress syndrome (ARDS), infant respiratory distress syndrome (IRDS) and septicaemia is known to be associated with pulmonary intravascular, interstitial and intra-alveolar deposition of fibrin [1]. The formation of fibrin during injury and inflammatory reactions, followed by its clearance during the repair process, is the result of a dynamic interplay between coagulant and fibrinolytic factors which amongst other cells are synthesized by peripheral blood monocytes, lung alveolar macrophages (AM) and lung interstitial macrophages [2][3][4]. Tissue factor (TF), which is produced by mononuclear phagocytes, is a receptor for coagulation factor VII [5] and plays an important role in the initiation of intravascular and extravascular coagulation leading to fibrin generation [2,3]. Owing to their expression of strong procoagulant (TF) activity, monocytes and AM represent foci for the deposition of fibrinogen and/or fibrin in vivo [6] and in vitro [7,8]. Binding of fibrinogen to specific receptors on blood monocytes has also been postulated to play a specific role in the differentiation of monocytes into macrophages [9]. Both monocytes and AM express β 2 -integrins (CD11b/CD18 and CD11c/CD18) on the cell surface which, in addition to mediating intercellular adhesion [10], have been shown to bind fibrinogen and factor X [11][12][13]. Coordinated membrane expression of procoagulant activity (TF) and receptors for coagulation factors (CD11b/CD18 and CD11c/CD18) would facilitate fibrin deposition when plasma factors and cofactors are supplemented. It is not known, however, whether these molecules are presented in a concerted fashion on the cell surface or whether they are independently regulated. Blood monocytes and AM are both members of the same cell differentiation (monocyte) lineage, but they are normally exposed to a different local milieu. It was, therefore, of interest to compare their response to the biologically highly active stimulant lipopolysaccharide (LPS), which in vivo is a potential candidate for cell stimulation during systemic pathological conditions such as septicaemia, but also locally when micro-organisms are introduced via the respiratory tract. LPS is a bacterial product of the outer membrane of Gram-negative bacteria which exerts its effects both directly, but also indirectly via the release of proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. The intention of this study was, therefore, to compare the baseline expression of TF and β 2 -integrins on blood monocytes and AM and to examine the changed expression induced by LPS challenge. Materials and methods Bronchoalveolar lavageBronchoalveolar lavage (BAL) was performed in healthy, nonsmoking volunteers with normal lung function Expression of leukocyte integrins and tissue factor in mononuclear phagocytes. B. Nakstad, T. Haugen, O.H. Skjønsberg, T. Lyberg. ©ERS Journals Ltd 1998.ABSTRACT: Coagulation is intimately involved in the pathology of inflammation. The leukocyt...

Macrophages Synthesize Factor X and Secrete Factor X/Xa-containing Prothrombinase Activity into the Surrounding Medium

“…The actual procoagulant expressed by a defined macrophage/monocyte population may vary dependent on the differentiation state of the cell and on the type of inflammatory stimulus employed. Although tissue factor is by far the best documented and most frequently studied monocyte/macrophage procoagulant (1,(8)(9)(10)(11)(12)(13)(14)(15), several other compo-nents of the coagulation cascade are known to be expressed by monocytes/macrophages. It has been shown that human lung macrophages display Factor VII-like activity and contain Factor VII mRNA (16,17).…”

Cell specific control of coagulation and fibrinolysis within the lung

“…Macrophages retrieved by bronchoalveolar lavage may not be representative of those that remain adherent to the alveolar epithelium. Such differences may be explainable by the known relationships between integrin expression, cell adherence, and macrophage phenotype (41).…”