Granuloma formation by synthetic bacterial cell wall fragment: muramyl dipeptide

Nagao

Imai

et al. 1980

A synthetic bacterial cell wall constituent, muramyl dipeptide (MDP), was found to induce the enhancement of macrophage spreading and attachment on glass or plastic surfaces. Macrophages exposed to bacterial lipopolysaccharide or lymphokine-containing cell supernatants showed similar enhancement. This finding supports the view that MDP activates macrophages. MDP was also found to enhance the viability of macrophages but to inhibit 3H-thymidine incorporation by macrophages.

Section: Effect Of Mdp On 3h-thymidine Uptake By Macrophagesmentioning

confidence: 99%

Macrophage Activation by Muramyl Dipeptide as Measured by Macrophage Spreading and Attachment

Nagao

Imai

et al. 1980

“…A muramyl dipeptide (MDP), N-acetylmuramyl-L-alanyl-n-isoglutamine, in bacterial cell walls is an essential structure for their diverse biological activities including an immunoregulatory capacity (3). We and other investigators have found, with different parameters, that MDP activates macrophages (6,7,II,14,18,19,20,21). We suggested further that the activation of macrophages by MDP as assayed by macrophage migration inhibition does not require lymphocyte participation (9,24).…”

mentioning

confidence: 99%

Macrophage Activation by Muramyl Dipeptide (MDP) without Lymphocyte Participation

Nagao

Miki

1981

An increase in the numbers of spread macrophages caused by macrophage stimulants was found to be a very sensitive measure for macrophage activation. Muramyl dipeptide (MDP), bacterial lipopolysaccharide (LPS), and lymphokines were found to activate macrophages dose-dependently as measured by this parameter. Macrophage activation by MDP was strictly dependent on its adjuvant-active stereochemically specific structures. Macrophage activation by MDP and LPS occurred without lymphocyte participation. It is suggested that LPS also activates macrophages via lymphocytes.A muramyl dipeptide (MDP), N-acetylmuramyl-L-alanyl-n-isoglutamine, in bacterial cell walls is an essential structure for their diverse biological activities including an immunoregulatory capacity (3). We and other investigators have found, with different parameters, that MDP activates macrophages (6,7, II,14,18,19,20,21). We suggested further that the activation of macrophages by MDP as assayed by macrophage migration inhibition does not require lymphocyte participation (9,24). However, there are some reports suggesting that MDP does not activate macrophages (8, 16) but does activate lymphocytes (8,15,16,22).Conflicting data have also been reported concerning the requirement of lymphocytes for macrophage activation by a bacterial lipopolysaccharide (LPS), a substance strikingly similar to MDP in its biological activities. Activation measured by tumoricidal capacity (5) does not require lymphocytes, whereas B lymphocytes are required for activation measured by glucosamine uptake (23). When measured by macrophage glucose utilization, however, LPS activates macrophages without lymphocytes just as well as in the presence of lymphocytes (13).To gain further insight into the mechanisms of macrophage activation by MDP, we compared macrophage activation by MDP with that by LPS or lymphokine and examined further the question of whether lymphocytes are required for macrophage activation by MDP. In this study, we used as parameters macrophage attachment and spreading on a plastic surface, which we have recently found to be sensitive and reliable indications of macrophage activation (17). We found that MDP activates guinea pig peritoneal exudate macrophages without lymphocyte involvement.

“…In parallel with these findings, a variety of biological activities of MDP have been observed and shown to depend on the same specific structure (6,31,34). In vivo, MDP has been reported to possess pyrogenicity (16), stimulatory effect on the reticuloendothelial system (35), granulomatogenicity in several animals (10,32) and arthritogenicity in the rat (22). To further study the mechanism of such in vivo effects of MDP, a target cell for MDP has been searched for and different types of immune cells including macrophages and T-and B-cells have been implicated (11,22,29,34,38).…”

mentioning

confidence: 87%

Effect of Muramyldipeptide, a Synthetic Bacterial Adjuvant, on Enzyme Release from Cultured Mouse Macrophages

Imai

1981

Monolayer cultures of macrophages obtained by peritoneal lavage of normal or thioglycollate-stimulated mice spontaneously secreted lysosomal enzymes into the culture medium. When the elicited macrophages were cultured in the presence of muramyldipeptide (MDP), a 20-30% increase in the release of P-glucuronidase was consistently observed and the intracellular activity decreased to about 45% of that of control cells after 6-8 days' culture. A stimulatory effect ofMDP on lysozyme secretion, though less profound, was also observed. In contrast, release of neither enzyme was stimulated in resident macrophages by the addition of MDP. A neutral a-glucosidase, which has recently been found to localize also in granules of macrophages, remained inside the cells and neither its activity nor its release was affected by the addition ofMDP to either type of macrophages. A large amount of lactic dehydrogenase was released only when the resident, not the elicited, macrophages were cultured for 3--4 days and then phagocytosed zymosan.Muramyldipeptide (MDP, N-acetylmuramyl-L-alanyl-n-isoglutamine) has the minimal structure for adjuvant activity of bacterial cell walls (9, IS). With the aid of chemical synthesis of this compound and its analogs, a very high stereospecificity for adjuvant activity has been found in several systems (I, 3, 16, 17). In parallel with these findings, a variety of biological activities of MDP have been observed and shown to depend on the same specific structure (6,31,34). In vivo, MDP has been reported to possess pyrogenicity (16), stimulatory effect on the reticuloendothelial system (35), granulomatogenicity in several animals (10,32) and arthritogenicity in the rat (22). To further study the mechanism of such in vivo effects of MDP, a target cell for MDP has been searched for and different types of immune cells including macrophages and T-and B-cells have been implicated (11,22,29,34,38).In vitro, MDP has such diverse effects on macrophages as migration inhibition (23), stimulation of attachment and spreading (33), enhancement of [1_14C]glucose oxidation (14), collagenase secretion (37), and superoxide production (25). Thus increasing lines of evidence for macrophage activation by MDP have now accumulated in several labolatories. The in vivo effect of MDP on macrophages so far studied resembles that of lymphokines or migration inhibition factor (MIF) and 51