Scavenger receptor-mediated delivery of muramyl dipeptide activates antitumor efficacy of macrophages by enhanced secretion of tumor-suppressive cytokines

Srividya, S.; Roy, Rajendra P.; Basu, Sandip K.; Mukhopadhyay, Asok

doi:10.1002/jlb.67.5.683

Cited by 17 publications

(15 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enhanced SR-mediated delivery of MDP into M by chemical conjugation of polyanions has been shown to increase its biological response, inducing high levels of inflammatory mediators and enhanced macrophage tumoricidal activity. 42,43 We have shown that SR-A and MARCO are specific receptors for MDP and are required for the NOD2-mediated cellular response ( Figure 5). The role of NOD2 in neisserial disease is relatively underinvestigated compared with TLRs.…”

Section: Discussionmentioning

confidence: 99%

SR-A/MARCO–mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens

Mukhopadhyay

Varin

Chen

et al. 2011

Blood

110

View full text Add to dashboard Cite

Phagocytic and pathogen sensing receptors are responsible for particle uptake and inflammation. It is unclear how these receptors' systems influence each other's function to shape an innate response. The class-A scavenger receptors SR-A (scavenger receptor A) and MARCO (macrophage receptor with collagenous structure) are 2 well-characterized phagocytic receptors that are unable to initiate inflammatory responses by themselves, yet are implicated in the pathogenesis of various inflammatory disorders. However, the mechanism for such an apparent discrepancy is still unclear. We utilized SR-A IntroductionInnate immune recognition of microbes by pattern recognition receptors (PRRs) initiates 2 distinct effector responses, phagocytosis and inflammation, to promote pathogen clearance, killing, tissue repair, and induction of adaptive immunity. 1 Phagocytic PRRs, such as scavenger receptors, and pathogen sensors, such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), mediate uptake and initiate inflammation, respectively. 2,3 Although much has been learned about these 2 processes separately, knowledge is still limited on how these processes are coordinated during the host response. Functional collaboration between innate receptor families must exist to coordinate uptake and inflammation; breakdown in such receptor collaboration can lead to defective pathogen clearance and inflammatory pathologies. 4 The scavenger receptor A (SR-A) and macrophage receptor with collagenous structure (MARCO) are 2 well-characterized, nonopsonic phagocytic receptors on myeloid cells. 5,6 Due to their shared multidomain structure and their ability to bind modified low-density lipoprotein and other polyanionic ligands (a common feature of all scavenger receptors), they are defined as members of the class-A scavenger receptor family. Both molecules are multiligand, multifunctional receptors 7 ; share large numbers of overlapping but distinct polyanionic ligands; and carry out common functions such as cellular adhesion, 8 migration, 9 phagocytosis, and antigen presentation. 10 Both receptors have been shown to bind a range of isolated microbial components 11-14 and intact Grampositive and Gram-negative organisms, 15,16 and their nonredundant role in host defense has been established in a variety of bacterial infection models. [17][18][19][20] Although SR-A and MARCO recognize a range of highly inflammatory ligands, these receptors by themselves are unable to initiate inflammatory signaling, which is usually triggered by sensing PRRs that share overlapping ligand repertoires. However, SR-A and MARCO have been implicated in the pathogenesis of a range of chronic and acute inflammatory pathologies, including atherosclerosis, Alzheimer disease, granuloma formation, and septic shock. 21 Studies utilizing both microbial and sterile inflammatory stimuli and distinct models of inflammation have suggested both proinflammatory and anti-inflammatory roles; however, the mechanisms for such apparent discrepancies are unknown. Therefore, how SR-A...

show abstract

Section: Discussionmentioning

confidence: 99%

SR-A/MARCO–mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens

Mukhopadhyay

Varin

Chen

et al. 2011

Blood

110

View full text Add to dashboard Cite

show abstract

“…Preparation of MBSA-MDP conjugates MDP was conjugated to BSA by using water-soluble carbodiimide in the presence of N-hydroxysulfosuccinimide as described previously (Srividya et al, 2000). Briefly, 10 mg of the MDP was incubated in the presence of 3.6 mg of EDC and 3.2 mg of sulfo-NHS in 0.1 ml of water for 10 minutes at room temperature to generate an active ester of MDP.…”

Section: Antibodies and Recombinant Proteinsmentioning

confidence: 99%

“…To determine the effect of MBSA-MDP on Salmonella-infected macrophages, MBSA was conjugated with MDP using a water-soluble carbodiimide (Srividya et al, 2000). Subsequently, J774E macrophages were cultured in the presence of various concentrations of MBSA-MDP or free MDP for 12 hours, then washed and infected with Salmonella typhimurium at a ratio of 1:10 (macrophage:Salmonella).…”

Section: Reconstitution Of Phagosome-lysosome Transport In Permeabilimentioning

confidence: 99%

“…Recently, we reported that intracellular delivery of MDP to macrophages through scavenger receptor (SCR)-mediated endocytosis triggers the secretion of different cytokines (Srividya et al, 2000). Several independent studies have shown that activation of macrophages through different cytokines alone or in concert can contribute to the antimycobacterial potential of these cells, resulting in the control of infection in vitro (Rook et al, 1986;Chan et al, 1992;Flynn et al, 1995;Schaible et al, 1998;Via et al, 1998).…”

Section: Reconstitution Of Phagosome-lysosome Transport In Permeabilimentioning

confidence: 99%

“…Possibly, higher expression of Rab7 in MBSA-MDP-treated cells than in untreated or MDP-treated cells correlates with the SCRmediated enhanced uptake of MDP by macrophages (Mukhopadhyay et al, 1989;Majumdar et al, 1991). It is tempting to speculate that the enhanced secretion of various cytokines by MBSA-MDP-treated cells (Srividya et al, 2000) regulates the expression of the Rab proteins. This is supported by a recent finding that macrophages treated with IFN-γ induced Rab5 expression (Alvarez-Dominguez et al, 1998).…”

Section: Reconstitution Of Phagosome-lysosome Transport In Permeabilimentioning

confidence: 99%

See 2 more Smart Citations

Diverting intracellular trafficking ofSalmonellato the lysosome through activation of the late endocytic Rab7 by intracellular delivery of muramyl dipeptide

Mukherjee

Parashuraman

Krishnamurthy

et al. 2002

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Previously, we showed that live Salmonella-containing phagosomes(LSP) recruit early acting Rab5 and promote fusion with early endosomes, thus avoiding transport to the lysosomes. Therefore, live Salmonellasurvive in a specialized compartment. Here we show that scavenger-receptor-mediated intracellular delivery of muramyl dipeptide (MDP)to macrophages leads to efficient killing of Salmonella both in vitro and in vivo. To understand the intracellular trafficking modulation of Salmonella by delivery of MDP, we investigated the levels of endocytic Rab proteins, which are the major regulators of vesicular transport. Western blot analysis reveals reduced Rab5 and enhanced Rab7 content in the maleylated bovine serum albumin-MDP (MBSA-MDP)-treated cells. The reduced content of Rab5 in the treated cells and on phagosomes inhibits the fusion of Salmonella-containing phagosomes with early endosomes, and the enhanced Rab7 content in these cells facilitated targeting of LSP to lysosomes, which contain cathepsin D and vacuolar ATPase, for killing. In vitro reconstitution of lysosomal transport demonstrated that a reduced content of Rab5 and an enhanced level of Rab7 in MBSA-MDP-treated cells is primarily responsible for targeting Salmonella to lysosomes. Intracellular delivery of MDP thus offers a general strategy against macrophage-associated infections caused by intracellular pathogens that survive in the host cell by resisting transport to lysosomes.

show abstract

Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy

Nabergoj

Mlinarič-Raščan

Jakopin

2018

Medicinal Research Reviews

View full text Add to dashboard Cite

In the last decade, cancer immunotherapy has emerged as an effective alternative to traditional therapies such as chemotherapy and radiation. In contrast to the latter, cancer immunotherapy has the potential to distinguish between cancer and healthy cells, and thus to avoid severe and intolerable side‐effects, since the cancer cells are effectively eliminated by stimulated immune cells. The cytosolic nucleotide‐binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are important components of the innate immune system and constitute interesting targets in terms of strengthening the immune response against cancer cells. Many NOD ligands have been synthesized, in particular NOD2 agonists that exhibit favorable immunostimulatory and anticancer activity. Among them, mifamurtide has already been approved in Europe by the European Medicine Agency for treating patients with osteosarcoma in combination with chemotherapy after complete surgical removal of the primary tumor. This review is focused on NOD receptors as promising targets in cancer immunotherapy as well as summarizing current knowledge of the various NOD ligands exhibiting antitumor and even antimetastatic activity in vitro and in vivo.

show abstract

Scavenger receptor-mediated delivery of muramyl dipeptide activates antitumor efficacy of macrophages by enhanced secretion of tumor-suppressive cytokines

Cited by 17 publications

References 48 publications

SR-A/MARCO–mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens

SR-A/MARCO–mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens

Diverting intracellular trafficking ofSalmonellato the lysosome through activation of the late endocytic Rab7 by intracellular delivery of muramyl dipeptide

Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy

Contact Info

Product

Resources

About