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P H Koo

Publications and source records attributed to P H Koo.

At least 19 recordsLinked to original sources
PubMed2000

alpha2-macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14.

Human placental protein 14 (PP14; also known as glycodelin and progesterone-associated endometrial protein) is an immunosuppressive protein of the lipocalin structural superfamily. Mechanisms regulating serum PP14's immunosuppressive activity remain to be elucidated. In the present study, an interaction between PP14 and a major serum protein carrier, alpha(2)-macroglobulin (alpha(2)M), was documented for the first time. Using native gel electrophoresis, we showed that PP14, as well as its alternative splice variant PP14.2, binds to both alpha(2)M and methylamine-activated (MA)-alpha(2)M. Cross-competition studies demonstrated that the variants compete for binding to alpha(2)M. PP14 bound to alpha(2)M and MA-alpha(2)M with K(d) values of 167+/-70 and 221+/-56 nM (means+/-S.D.) respectively, as determined by surface plasmon resonance. Significantly, the addition of alpha(2)M or MA-alpha(2)M to a T-cell proliferation assay strongly potentiated the inhibitory capacity of PP14. On the basis of these findings, alpha(2)M emerges as the first serum protein that can physically associate with, and thereby regulate, PP14. Moreover, this represents the first documented interaction between the protein carrier alpha(2)M and a lipocalin protein.

Binding, Competitive↗
PubMed2000

Rat alpha1-macroglobulin enhances nerve growth factor-promoted neurite outgrowth, TrkA phosphorylation, and gene expression of pheochromocytoma PC12 cells.

Monoamine-activated human alpha2-macroglobulin (alpha2M) has been previously demonstrated to inhibit TrkA-, TrkB-, and TrkC-mediated signal transduction. Rat alpha1-macroglobulin (alpha1M) and alpha2M are structural homologues of human alpha2M, but rat alpha1M is distinctly different from rat alpha2M in many ways and its role in the mammalian nervous system is unknown. In this report, monoamine-activated rat alpha1M was demonstrated to enhance in a dose-dependent manner nerve growth factor (NGF)-promoted neurite outgrowth in pheochromocytoma PC12 cells. Monoamine-activated alpha1M by itself, however, was neither neurotrophic nor mitogenic to PC12 cells. To investigate further its possible mode of action, the ability of monoamine-activated alpha1M and normal alpha1M to bind and to activate the NGF receptor (TrkA) was investigated. Monoamine-activated alpha1M formed a more stable complex with TrkA than normal alpha1 M, but the binding of monoamine-activated alpha1M to TrkA was adversely affected by prior stimulation of TrkA with NGF. In addition, monoamine-activated alpha1M enhanced the NGF-promoted TrkA phosphorylation and up-regulated the expression of NGF-inducible immediate-early genes (c-jun and NGFI-A) and delayed-response genes (SCG10 and transin) in PC12 cells; normal alpha1M, in contrast, produced little or no effect. This study demonstrates that alpha1M, the constitutive form of alpha-macroglobulin in the rat, possesses the ability to promote NGF-mediated differentiation in PC12 cells, possibly via its direct action on TrkA receptors and TrkA-mediated signal transduction and gene expression.

Animals↗
PubMed1999

Rat alpha(2)-macroglobulin inhibits NGF-promoted neurite outgrowth, TrK phosphorylation, and gene expression of pheochromocytoma PC12 cells.

Rat alpha-1-macroglobulin (alpha(1)M) and alpha-2-macroglobulin (alpha(2)M) are murine homologs of human alpha(2)M, and rat alpha(2)M is generally known as an acute-phase protein. Monoamine-activated forms of human alpha(2)M have been shown to inhibit various neuronal functions, but the effect of rat alpha(1)M and acute-phase alpha(2)M on neurons is largely unknown. In this report, rat serotonin-activated alpha(2)M (5HT-alpha(2)M) has been demonstrated to inhibit nerve growth factor (NGF)-promoted neurite extension in pheochromocytoma PC12 cells, and we investigated its possible mechanism of action including its effect on NGF-promoted signal transduction and gene expression in these cells. Especially in the absence of NGF, 5HT-alpha(2)M was found to bind to TrkA (the high-affinity receptor for NGF) much better than normal alpha(2)M (N-alpha(2)M). 5HT-alpha(2)M dose-dependently inhibited NGF-promoted autophosphorylation of TrkA, and decreased the expression of two immediate-early genes (NGFI-A and c-jun) and two delayed-response genes (SCG10 and transin) which are associated with neurite outgrowth in PC12 cells. The unmodified N-alpha(2)M, on the other hand, exhibited very little or no inhibitory effects on neurite extension, Trk phosphorylation, or expression of these genes. The results of this study taken together suggest that monoamine-activated acute-phase rat alpha(2)M appears to inhibit neurite outgrowth in PC12 cells possibly via its direct binding to TrkA and subsequent blocking of TrkA-mediated signal transduction and gene expression.

Adrenal Gland Neoplasms↗
PubMed1998

Inhibition of dopamine and choline acetyltransferase concentrations in rat CNS neurons by rat alpha 1- and alpha 2-macroglobulins.

Previous studies have implicated human alpha-2-macroglobulin (alpha2M) as a potential regulator of neuronal development and function. Rat alpha-1-macroglobulin (alpha1M) and acute-phase alpha-2-macroglobulin (alpha2M) are murine homologues of human alpha2M. In this report, we tested the effect of intracranially infused serotonin-activated rat alpha1M (5HT-alpha1M) on the concentration of dopamine (DA) in the corpus striatum in vivo and the effect of 5HT-activated rat alpha1M and alpha2M on the choline acetyltransferase (ChAT) activity upon embryonic basal forebrain neurons in culture. The results show that direct infusion of 0.65 nmole rat 5HT-alpha1M into the adult rat corpus striatum produced a consistent attenuation upon striatal DA concentrations. This decrease was particularly prominent at 5-7 days post-infusion. In addition, rat 5HT-alpha1M and rat 5HT-alpha2M, like human 5HT-alpha2M, all significantly inhibited ChAT activity of embryonic rat cerebral cortex neurons. Although normal human alpha2M and rat alpha2M were either marginally or insignificantly inhibitory in this preparation, normal rat alpha1M dose-dependently inhibited ChAT activity. These results demonstrate that monoamine-activated alpha-macroglobulins from rat depress dopaminergic and cholinergic neurotransmitter systems in the CNS, and this suggests a potential regulatory role of these alpha-macroglobulins in neurotransmitter metabolism.

Animals↗
PubMed1998

Inhibition of phosphorylation of TrkB and TrkC and their signal transduction by alpha2-macroglobulin.

Monoamine-activated alpha2-macroglobulin (alpha2M) was shown to reduce the dopamine concentration in corpus striatum of adult rat brains and inhibit other neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor, neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for dopaminergic neurons, the effect of monoamine-activated alpha2M on signal transduction by trkB and trkC was investigated. The results show that monoamine-activated alpha2M binds to trkB and inhibits brain-derived neurotrophic factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma SH-SY5Y cells. Monoamine-activated alpha2M also blocks tyrosine phosphorylation of phospholipase C-gamma1 and extracellular signal-regulated protein kinase (ERK)-1, which are key intracellular proteins involved in trkB signal transduction. Similarly, monoamine-activated alpha2M inhibits tyrosine phosphorylation of neurotrophin-3-induced trkC and its signal transduction in a dose-dependent manner in NIH3T3 cells expressing trkC (NIH3T3-trkC). In contrast to monoamine-activated alpha2M, normal alpha2M has little or no significant inhibitory effect on the phosphorylation of trkB and trkC. In addition, the retinoic acid-promoted tyrosine phosphorylation of phospholipase C-gamma1, ERK-1, and/or ERK-2 in SH-SY5Y cells was unaffected by monoamine-activated alpha2M; this suggests that the inhibitory effect of activated alpha2M on the neurotrophin-stimulated phosphorylation of intracellular signalling proteins may be specific. Taken together, the data indicate that activated alpha2M is a pan-trk inhibitor, which by virtue of its binding to trk receptors may block trk-mediated signal transduction in dopaminergic neurons and lead to reduction of dopamine concentration in corpus striatum.

3T3 Cells↗
PubMed1996

Inhibition of long-term potentiation development in rat hippocampal slice by alpha 2-macroglobulin, an acute-phase protein in the brain.

Alpha-2-macroglobulin (alpha 2M) in the rat and human brain is an acute-phase protein synthesized primarily by astrocytes, and it has been implicated in Alzheimer's disease and other neuropathological processes. The activated forms of alpha 2M, but not the native form, can suppress the neurite outgrowth of the central neurons, presumably through binding to neurotrophic factors and through direct inhibition of neurotrophic factor receptor signal transduction. Since neurotrophic factors are known to be involved in synaptic plasticity, we tested the effect of both the native and methylamine-activated (MA-alpha 2M) forms of alpha 2M on long-term potentiation (LTP) in area CA1 of adult rat hippocampal slice. Neither native alpha 2M nor MA-alpha 2M had an effect on baseline synaptic transmission. LTP induced by 200-Hz trains in the presence of 1.4 microM or 0.14 microM native alpha 2M was indistinguishable from control LTP. Although the presence of MA-alpha 2M at the same concentrations did not interfere with LTP induction, the development and maintenance of potentiation was blocked in a concentration-dependent time course. Results of this study indicate that the accumulation and activation of alpha 2M with inflammatory neuropathologies such as Alzheimer's disease can inhibit synaptic plasticity, which might partly account for the memory deficits seen in these patients.

Animals↗
PubMed1996

Alteration of dopamine release by rat caudate putamen tissues superfused with alpha 2-macroglobulin.

Monoamine-activated alpha-2-macroglobulin (alpha 2M) has been shown to decrease the dopamine concentrations in rat caudate putamen (CP) in vivo as well as inhibit choline acetyltransferase activities in the culture of basal forebrain neurons. In this study, we further investigated the effects of methylamine-activated alpha 2M (MA-alpha 2M) upon striatal dopaminergic function by determining whether a direct infusion of this glycoprotein will alter dopamine (DA) release in vitro from superfused CP tissue fragments. In experiment 1, an infusion of 2.8 microM MA-alpha 2M produced a statistically significant increase in DA release compared with control superfusions. In experiment 2, varying doses (0, 0.7, 1.4, 2.8, 4.1 microM) of MA-alpha 2M were tested for their capacity to alter DA release. Only the 2.8 microM dose of MA-alpha 2M was effective in producing a significant increase of DA release. In experiment 3, the normal form of alpha 2M (N-alpha 2M) at 2.8 microM was compared with the control superfusions. The infusion of N-alpha 2M produced an increase in DA release which was substantially lower than the DA increase induced by MA-alpha 2M, and not significantly different from that of the control superfusion. These results show that MA-alpha 2M, like some other neurotoxins, can markedly alter CP dopaminergic function as indicated by the acute increase in DA release following infusion of this glycoprotein, and these effects are exerted at a relatively narrow range of doses. Taken together, these data suggest that this glycoprotein, if allowed to accumulate in the central nervous system (CNS), may promote some neurodegenerative changes that can occur in disorders like Parkinson's disease.

Alzheimer Disease↗
PubMed1994

Intracranial infusion of monoamine-activated alpha 2-macroglobulin decreases dopamine concentrations within the rat caudate putamen.

Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit choline acetyltransferase in basal forebrain neurons as well as neurotrophin-dependent neuronal functions. The objective of this study was to determine whether monoamine-activated alpha 2M can affect the caudate putamen (CP) dopaminergic system in vivo. Male rats received intracranial infusions of methylamine-activated alpha 2M (0.6 nmole) and contralateral infusions of its vehicle, phosphate-buffered saline (PBS). Five days following infusion, the animals were killed, the CP dissected into three rostral-caudal segments, and assayed for dopamine (DA) using a high-performance liquid chromatography system. Within the two rostral CP segments (the approximate site of cannula placement), statistically significant (26%) reductions of DA concentrations were obtained on the alpha 2M-infused side of the CP with 90-100% of the animals showing decreases. At a more distal (caudal) site of the CP, DA concentrations showed only an insignificant (12%) reduction. No differences in DA concentrations between sides infused with bovine serum albumin versus PBS or from olfactory tubercle samples were obtained in these animals. These results demonstrate that monoamine-activated alpha 2M is capable of producing significant degeneration of the nigrostriatal dopaminergic system in vivo and suggest that this factor may play a role in age-related neurodegenerative disorders such as Parkinson's disease.

Animals↗
PubMed1994

Monoamine-activated alpha 2-macroglobulin inhibits choline acetyltransferase of embryonic basal forebrain neurons and reversal of the inhibition by NGF and BDNF but not NT-3.

Monoamine-activated alpha 2-macroglobulin (alpha 2M) has recently been shown to inhibit the growth and survival of cholinergic neurons of the basal forebrain (Liebl and Koo: J Neurosci Res 35:170-182, 1993). The mechanism of this inhibitory effect is believed to involve the regulation of growth factor activities by alpha 2M. The objectives of this study are to determine whether monoamine-activated alpha 2M can inhibit choline acetyltransferase (ChAT) activity of cholinergic basal forebrain neurons, and whether some common neurotrophins in the CNS can reverse the inhibition. This study demonstrates that both methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) can dose-dependently suppress the expression of normal basal levels of ChAT activity in embryonic rat basal forebrain cells in vitro, while normal alpha 2M has little or no effect. As little as 0.35 microM monoamine-activated alpha 2M can suppress the ChAT activity, whereas either nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), but not neurotrophin-3 (NT-3), stimulates ChAT expression of these cells. The addition of either NGF or BDNF to the alpha 2M-suppressed cells can increase ChAT activity back to its normal levels, while NT-3 can not. These results demonstrate that (1) monoamine-activated alpha 2M is a potent non-cytotoxic inhibitor of the ChAT activity in cholinergic basal forebrain neurons, and (2) NGF and BDNF are capable of not only stimulating the ChAT activity but can also specifically reverse the alpha 2M inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction.

Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit beta-nerve growth factor (NGF)-promoted neurite outgrowth and the survival of embryonic sensory and forebrain neurons, whereas normal alpha 2M has little or no such activity. The objective of this study is to elucidate the mechanism of inhibition by monoamine-activated alpha 2M. Methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) dose dependently inhibit NGF-promoted neurite outgrowth of the pheochromocytoma PC12 cell and its subline PC12(6-24) which overexpresses human trk protooncogene product, but have no effect on their viability, and this inhibition can be blocked by high concentrations of NGF. The binding of MA-alpha 2M to trk, which is a part of high-affinity NGF receptor, was studied with PC12(6-24) cells and NIH-3T3 fibroblasts expressing trk (trk-3T3). In each case MA-alpha 2M readily forms stable complexes with trk in vivo, whereas normal alpha 2M does not. Both 5HT-alpha 2M and MA-alpha 2M also dose dependently block NGF-promoted autophosphorylation of trk in vivo, whereas normal alpha 2M and plasmin-reacted alpha 2M are inactive or much less active. MA-alpha 2M also blocks NGF-promoted incorporation of 32P from [32P]ATP into trk receptors in vitro. Neither MA-alpha 2M, 5HT-alpha 2M, nor normal alpha 2M, however, blocks either platelet-derived growth factor-stimulated or epidermal growth factor-stimulated tyrosine phosphorylation of the respective receptors. Tyrosine phosphorylation of two of the intracellular substrates, phospholipase C-gamma 1 and extracellular signal-regulated kinase-2, in the NGF-promoted pathways is also dose dependently blocked by MA-alpha 2M. However, by comparison MA-alpha 2M is more effective in inhibiting the activation of phospholipase C-gamma 1 than trk. We conclude that monoamine-activated alpha 2M may block neurite outgrowth and neuronal survival by its specific binding to NGF receptors, thus inhibiting the NGF-promoted activation of intracellular second messenger pathways.

Adrenal Gland Neoplasms↗
PubMed1993

Comparative binding of neurotrophins (NT-3, CNTF and NGF) and various cytokines to alpha 2-macroglobulin.

All the nine common cytokines in this study (including NT-3, IGF-1, CNTF and TGF-alpha) bind noncovalently, yet with different specificities and to different degrees, with both normal alpha 2-macroglobulins (alpha 2M) and monoamine-modified alpha 2M. The binding of NGF is by far the most efficient and is least affected by cationic proteins. The binding of NT-3 is slightly affected by cationic proteins but is completely blocked by NGF. The binding of TGF-alpha, TGF-beta 1, CNTF, and IL-6 is severely blocked by cationic proteins/NGF. We conclude that NGF and NT-3 appear to bind specifically in significant quantities to the same alpha 2M sites; but the other cytokines by comparison bind minimally, and primarily or entirely use nonspecific molecular interactions in their binding to alpha 2M.

Animals↗
PubMed1993

Serotonin-activated alpha 2-macroglobulin inhibits neurite outgrowth and survival of embryonic sensory and cerebral cortical neurons.

Methylamine-modified alpha-2-macroglobulin (MA-alpha 2M) has been recently shown to inhibit the biological activity of beta-nerve growth factor (NGF) in promoting neurite outgrowth by embryonic dorsal root ganglia in culture (Koo PH, Liebl DJ, J Neurosci Res 31:678-692, 1992). The objectives of this study are to determine whether alpha 2M can also be modified by larger aromatic biogenic amines such as 5-hydroxytryptamine (5HT; serotonin), the nature of interaction between NGF and 5HT-modified alpha-2-M (5HT-alpha 2M), and the effect of 5HT-alpha 2M on the neurite extension and the growth of embryonic sensory and cholinergic neurons in 2 disparate animal species (chicken and rats). This study demonstrates that each mole of alpha 2M can combine with 15.2 +/- 1.8 moles of 5HT, in which up to 4.5 +/- 0.4 moles may be covalently bonded. As determined by gel filtration and polyacrylamide gel electrophoresis studies, both 5HT-alpha 2M and normal alpha 2M combine noncovalently with NGF, but 5HT-alpha 2M by comparison can combine with NGF somewhat more effectively. In contrast to normal alpha 2M, 5HT-alpha 2M at concentrations greater than about 0.17 microM exerts a dose-dependent inhibition on the NGF-stimulated neurite outgrowth by embryonic dorsal root ganglia and dissociated cells in culture, and the inhibitory effect can be overcome by higher NGF concentrations. Both 5HT-alpha 2M and MA-alpha 2M at 1.0 microM inhibit neurite extension by embryonic rat cerebral cortical cells and seriously damage these cells in culture. Such neurite-inhibitory activity, however, can only be partially blocked by extraneously added NGF alone. Normal alpha 2M (at 1.0 microM) and 5HT (at 188 microM), on the other hand, under the identical conditions produce very little or no effect on the normal cellular and axonal growth of these cells. We conclude that alpha 2M can potentially interact with nucleophilic monoamines, including neurotransmitters, to form inhibitory complexes which may inhibit/regulate NGF-promoted neurite outgrowth and neuronal survival. In addition, higher concentrations of such complexes can seriously damage certain CNS neurons which do not depend solely on NGF for survival.

Animals↗
PubMed1992

Inhibition of nerve growth factor-stimulated neurite outgrowth by methylamine-modified alpha 2-macroglobulin.

alpha 2-Macroglobulin (alpha 2M) is a rather ubiquitous protein in extracellular spaces of mammals. It is an inhibitor of endopeptidases, can be modified by aliphatic amines, and combines with a number of hormones/cytokines such as beta-nerve growth factor (NGF) [Koo PH, Stach RW (1989): J Neurosci Res 22:247]. The objective of this study is to compare the NGF-binding properties of methylamine-modified human alpha 2M (MA-alpha 2M) versus normal alpha 2M and their effects on the biological activity of NGF and neurite extension by embryonic chicken dorsal root ganglia. As determined by gel filtration, polyacrylamide gel electrophoresis, and equilibrium binding studies, these two forms of alpha 2M are similar in their binding affinities, with MA-alpha 2M binding about twice as much NGF as normal alpha 2M. Both normal alpha 2M and MA-alpha 2M combine noncovalently with NGF, and prior modification of alpha 2M is unnecessary for the binding to occur. In contrast to normal alpha 2M, MA-alpha 2M potently inhibits the biological activity of NGF and exerts a dose-dependent inhibition on the NGF-stimulated neurite outgrowth by embryonic chicken dorsal root ganglia in culture. The inhibitory effect of MA-alpha 2M can be overcome by higher NGF concentrations, but is irreversible at lower NGF concentrations. Trypsin-modified alpha 2M combines covalently and noncovalently with more NGF than normal alpha 2M but has very little neurite inhibitory activity. The mechanism of inhibition by MA-alpha 2M is discussed.

Animals↗
PubMed1989

Interaction of nerve growth factor with murine alpha-macroglobulin.

The murine nerve growth factor, when injected i.v. or, combined in vitro with plasma, was found largely associated with the mouse alpha-macroglobulin (a homologue of human alpha 2-macroglobulin). The nerve growth factor-alpha-macroglobulin complex produced is sufficiently stable to resist separation by gel filtration in 1.0 M sodium chloride, polyacrylamide gel electrophoresis, and immunoprecipitation by antibodies against alpha-macroglobulin. As determined by equilibrium binding studies and computer generated Scatchard analysis, alpha-macroglobulin apparently possesses two types of binding sites with the apparent dissociation constants of 1.2 x 10(-6) and 2.9 x 10(-9) M, respectively, saturable by 3.7 and 0.03 moles of nerve growth factor. Hence, about one mole of nerve growth factor is bound to each of the four subunits of alpha-macroglobulin. Nerve growth factor can be readily dissociated from alpha-macroglobulin in sodium dodecyl sulfate gel electrophoresis in the absence of a reductant. Procedures that affect the proteinase-binding or methylamine- activities of alpha-macroglobulin do not affect the binding of nerve growth factor, and the binding is unaffected by the presence of zinc ions or EDTA. Hence, nerve growth factor is noncovalently associated with alpha-macroglobulin at a site separate from that of the proteinase-, methylamine-, and zinc-binding sites of alpha-macroglobulin. Mouse alpha-macroglobulin can protect the nerve growth factor from inactivation by trypsin. Even in the presence of trypsin, alpha-macroglobulin-nerve growth factor complexes still can stimulate the neurite outgrowth by dorsal root ganglia of 9-day-old chicken embryos. Since alpha-macroglobulin can specifically and noncovalently carry nerve growth factor, one important role of this alpha-macroglobulin in the circulation and extracellular spaces may be to protect the nerve growth factor from proteinase inactivation.

Animals↗
PubMed1987

Mouse alpha-macroglobulin. Structure, function and a molecular model.

Mouse alpha-macroglobulin (M-AMG) is believed to be a functional homologue of human alpha 2-macroglobulin (h-alpha 2M). The subunit composition, the tryptic cleavage pattern before and after methylamine incorporation and the two-dimensional tryptic-peptide mapping, however, indicate that these two proteins are structurally distinct. M-AMG is composed of two major types of polypeptides (Mr 163,000 and 35,000) together with a minor polypeptide (Mr 185,000), whereas h-alpha 2M has only one type of polypeptide (Mr 185,000). After incorporation of methylamine, there is no change in the normal tryptic-cleavage pattern of M-AMG; however, tryptic cleavage of h-alpha 2M is severely retarded [Hudson & Koo (1982) Biochim. Biophys. Acta 704, 290-303]. The N-terminal sequence of the 163,000-Mr polypeptide of M-AMG shows sequence homology with the N-terminal sequence of h-alpha 2M. The amino acid compositions of M-AMG and its two major polypeptide chains are compared. Thermal fragmentation studies show that the 163,000-Mr polypeptide is broken down into 125,000-Mr and 29,000-Mr fragments. Trypsin-binding studies show that M-AMG can bind two molecules of trypsin/molecule. Inactivations of the trypsin-binding property of M-AMG and h-alpha 2M with methylamine show similar kinetics of inhibition at 4 degrees C. A structural model of M-AMG is proposed, based on accumulated data.

Amino Acids↗
PubMed1983

Human alpha 2-macroglobulin: a major serum factor cytotoxic for tumor cells.

Human alpha 2-macroglobulin (alpha 2M) was established here as a major serum factor which inhibits the DNA synthesis of a mouse ovarian tumor cell line in culture. This inhibitory activity was species non-specific, dose-dependent and unaffected by serum concentrations in culture. alpha 2 M was cytotoxic to both murine and human tumor cell lines in culture, as determined by 2 different viability staining techniques, morphological observation and long-term in vitro culture. This report implicates alpha 2 M or an alpha 2 M-associated substance as a major cytotoxic serum factor that may be involved in endogenous cancer control processes in mammalian species.

Animals↗