Lymphokine‐induced secretion of plasminogen activator by murine macrophages

Abstract

Thioglycollate-stimulated macrophages are known to release a plasminogen activator (PA) into the medium. In this study it was investigated whether macrophages could be activated to release PA after exposure to lymphokines. Macrophage monolayers obtained by 24 h culture of proteose peptone-elicited murine exudate cells were incubated with lymphocyte culture supernatants. After 48 h the supernatants were replaced by serum-free medium and the macrophages were incubated for another 24-48 h. These supernatants were assayed for PA as measured by the lysis of 125I-labeled fibrin. The following results were obtained: (a) Supernatants of antigen or mitogen-stimulated spleen cells induced PA secretion by macrophages whereas control supernatants were ineffective. The same was found with supernatants of mitogen-stimulated lymph node cells. (b) PA secretion by macrophages seems to be induced by a rather narrow concentration range of lymphokines. (c) Lymphokine-induced PA secretion by macrophages is enhanced after phagocytosis of latex beads. The results show that PA secretion by activated macrophages can be considered as a parameter of immunoactivation.

Role of infiltrated leucocytes in tumour growth and spread

“…Macrophages also indirectly enhance blood vessel formation by possessing a procoagulant activity through fibrin deposition (Mantovani et al, 1992). In addition, many macrophages produced factors, proteases and protease activators such as transforming growth factor-b (TGFb), platelet-derived growth factor, interleukin-6 (IL-6), urokinase plasminogen activator and Tissue-type Plasminogen Activator (t-PA) that may cause degradation of extracellular matrix to facilitate the tumour cell invasion and migration and induce angiogenesis (Egami et al, 2003;Eubank et al, 2003;Hildenbrand et al, 1995;Klimetzek and Sorg, 1977). Moreover, TAMs contribute greatly to the growth of the tumour by producing proangiogenic and tumour-stimulating chemokines such as CCR2 ligands (Vicari and Caux, 2002).…”

Induction of plasminogen activator secretion in macrophages by electrochemical stimulation of the hexose monophosphate shunt with methylene blue.

“…The triggering nature of the metabolic burst is indicated by the fact that it is sufficient to expose the cells to a stimulus-e.g., zymosan (1), sheep erythrocytes (1) or methylene blue-for the short period of 1 hr at the onset of culturing in order to obtain a secretory response that manifests itself 2-4 days later. Although our experiments do not prove that the metabolic burst and the secretion of plasminogen activator are (9), phorbol myristate acetate (9), and products of mitogentreated lymphocytes (10,11) have been reported to induce plasminogen activator secretion in macrophages, and HMP shunt stimulation is a common early effect of all these agents (12,13). In our own experiments on nonelicited mouse macrophages, similar degrees of shunt stimulation were obtained with 10 nM phorbol myristate acetate and with 100 ,M methylene blue.…”

Modulation of plasminogen activator secretion by activated macrophages: influence of serum factors and correlation with tumoricidal potential.

“…Other investigators have studied PA secretion as a correlate of macrophage activation (8)(9)(10). Klimetzek and Sorg (9) (20,21 (Table 1).…”

“…Normal macrophages do not secrete detectable plasminogen activator (PA) in vitro. Peritoneal macrophages activated in vitro by lymphokines or obtained in an activated state directly from mice with chronic infection secrete readily detectable PA in culture (9)(10)(11). We examined whether alterations in PA secretion by such activated macrophages occurs concomitantly with modulation of macrophage tumoricidal potential.…”