Cyclophosphamide augments ADCC by increasing the expression of Fc-receptors

Palermo, Marina S.; Giordano, Mirta; Serebrinsky, Graciela; Geffner, Jorge; Ballart, I. J.; Isturiz, Martı́n A.

doi:10.1016/0165-2478(87)90081-2

Cited by 14 publications

(7 citation statements)

References 22 publications

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“…Because both receptors are critically involved in ADCC, IFN-␥ might rather promote the contact between the PMNs and the target cell and hence the cytotoxic synapse formation than increase the availability of either perforin or granzyme B. 12,13,[34][35][36] This interpretation again fits with previous data that de novo synthesis of proteins is not required for ADCC. 10 Participation in ADCC might not be the only function of granzyme B.…”

Section: Discussionsupporting

confidence: 87%

Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils

Wagner

Iking‐Konert

Denefleh

et al. 2004

Blood

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Polymorphonuclear neutrophils (PMNs) produce an abundance of bactericidal and cytotoxic molecules consistent with their role as first-line defense against bacterial infection. PMNs, however, also cause efficient cellular cytotoxicity when targeted through Fc receptors to appropriate antibody-coated target cells. Although this so-called antibody-dependent cellular cytotoxicity (ADCC) was described many years ago, the mechanism of killing is still elusive. We now have found that PMNs contain perforin and granzyme B, the 2 molecules known as the cytotoxic entity of natural killer cells and of cytotoxic T lymphocytes as well. Lysates of PMNs were lytic for chicken erythrocytes in a time-, temperature-, and Ca 2؉ -dependent manner. Moreover, apoptosis of Jurkat cells was induced, consistent with the observation that the PMN lysates contain enzymatically active granzyme B. Taken together, our data provide evidence for the presence of perforin and granzyme B within the cytotoxic arsenal of PMNs.

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Section: Discussionsupporting

confidence: 87%

Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils

Wagner

Iking‐Konert

Denefleh

et al. 2004

Blood

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“…However, preclinical studies have suggested it is also possible that agents such as cyclophosphamide may actually enhance ADCC by up-regulating FCGRs. 33 Intriguingly, many studies have investigated ways to upregulate CD20 expression on CLL cells to further enable the ADCC mechanism of action of rituximab and intense research efforts have went into generating a new and improved IgG1 antibodies with increased affinity of the activating FCGRs. 34 Indeed, many of these antibodies have shown impressive in vitro ADCC activity and others have increased apoptosis, CDC, and ADCC to maximize potential benefit for the treatment of NHL and CLL.…”

Section: Discussionmentioning

confidence: 99%

Effect of FCGR2A and FCGR3A variants on CLL outcome

Dornan¹,

Spleiss

Yeh³

et al. 2010

Blood

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“…However, although it is known to be an alkylating agent, the mechanism of its therapeutic effect is unclear, and in some situations it may even augment immune responses. The administration of various doses of CY before sensitization increases delayed-type hypersensitivity (DTH) responses (16,17) and antibody-mediated cellular cytotoxicity (18) and enhances the expression of experimentally induced autoimmune diabetes (19). That CY promotes the development of diabetes in NOD mice is important to an understanding of pathogenesis in this model but is at odds with the clinical use of the drug in the treatment of autoimmunity.…”

mentioning

confidence: 99%

Cyclophosphamide-Induced Diabetes in NOD/WEHI Mice: Evidence for Suppression in Spontaneous Autoimmune Diabetes Mellitus

Charlton

Bacelj²,

Slattery³

et al. 1989

Diabetes

103

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Nonobese diabetic (NOD) mice spontaneously develop a lymphocytic infiltration of pancreatic islets (insulitis) that may progress to overt diabetes. Virtually all NOD/WEHI mice develop insulitis, but very few progress to diabetes. However, cyclophosphamide (CY) can promote the onset of diabetes in NOD mice, including the NOD/WEHI strain. The means by which CY produces diabetes was investigated in NOD/WEHI mice, in which it was hypothesized that active suppression mechanisms prevented the progression from insulitis to diabetes. A study of the time course of insulitis in the islets after CY was given showed that insulitis was initially reduced but rapidly increased over 16 days, and T-lymphocytes were predominant in the lesion. This suggested a compression of the normal time course of the disease seen in NOD mice. CY did not produce diabetes in any of 11 non-NOD strains studied. Fetal isografts in NOD mice given CY several days before were subjected to lymphocytic infiltration and beta-cell destruction. These findings suggested that CY was not directly beta-cell toxic and that altered beta-cells were not essential for beta-cell destruction. This was further demonstrated with subdiabetogenic doses of streptozocin, which significantly damaged beta-cells but did not increase the severity of insulitis or induce diabetes as did CY. Most important, the transfer of mononuclear cells from nondiabetic NOD mice to mice given CY prevented diabetes, which indicated that the likely effect of CY was via immunomodulation, possibly by allowing poised effector cells to act on beta-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cyclophosphamide augments ADCC by increasing the expression of Fc-receptors

Cited by 14 publications

References 22 publications

Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils

Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils

Effect of FCGR2A and FCGR3A variants on CLL outcome

Cyclophosphamide-Induced Diabetes in NOD/WEHI Mice: Evidence for Suppression in Spontaneous Autoimmune Diabetes Mellitus

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