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At least 19 recordsLinked to original sources

PubMed1991

A comparative study of [Leu1]Tuftsin and tuftsin, a natural phagocytosis-stimulating peptide.

1. [Leu1]tuftsin was reported to have greater phagocytosis-stimulating activity than tuftsin (Thr-Lys-Pro-Arg). 2. However, a study on inactivation of tuftsin by polymorphonuclear leukocytes (PMNs) demonstrated that leucine aminopeptidase, an ecto-enzyme, located on PMN surface was responsible for this mechanism. 3. Since leucine aminopeptidase is known to cleave Leu more easily than Thr at the N-terminal position of peptides, this suggested to us that [Leu1]tuftsin might then be inactivated by PMNs more easily than tuftsin, and thus this analog might be less active than tuftsin. 4. In addition, many tuftsin preparations used in earlier studies were not fully active, as high-performance liquid chromatography was not available to separate out many contaminating diastereomers. 5. In view of this, we have synthesized and purified [Leu1]tuftsin and compared its phagocytosis-stimulating activity with tuftsin. 6. Our results indicate that [Leu1]tuftsin is not as active as tuftsin in stimulating phagocytosis.

Amino Acid Sequence↗

PubMed1983

The similarity between tuftsin (Thr-Lys-Pro-Arg) receptors and tuftsin antibody: a case of induced molecular mimicry.

The characteristics of binding of tuftsin (Thr-Lys-Pro-Arg) and several of its synthetic analogues, to specific membrane receptors on rabbit polymorphonuclear granulocytes, were compared with the binding characteristics of rabbit specific antibody to tuftsin. [3H-Arg4]-tuftsin was used as the principal ligand. Six analogues were studied. Two of these, Thr-Lys-Pro and Ala-Lys-tuftsin-Glu-Ala3, showed no binding affinity either to receptor or antibody. Ala-Lys-tuftsin showed less binding than tuftsin to both acceptors. Three showed stronger binding than tuftsin. The order of binding among these was tuftsin ( [Glu]2-tuftsin ( [Pro-Pro3]-tuftsin (tuftsinyltuftsin. This same order of binding was found with both receptor and antibody.

Animals↗

PubMed1987

Tuftsin and tuftsin conjugates potentiate immunogenic processes: effects and possible mechanisms.

The immunoglobulin heavy chain associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity was found to augment the antigen presenting capacity of macrophages in culture when applied simultaneously with the antigen. To study the immunogenic effect of tuftsin in vivo the peptide was coupled covalently to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) antigens to form stable entities. Tuftsin-antigen conjugates were found to be very potent immunogens as tested by their capacity to increase antigen presentation in culture in primary and secondary responses. Thus, monolayers of macrophages pulsed in vitro with KLH-tuftsin conjugates exerted a stronger immunogenic effect than KLH alone. BSA, which by itself was not immunogenic, when applied to macrophages as tuftsin conjugate evoked a high lymphoproliferative immune response. In vivo, BSA conjugated to tuftsin, when injected in aqueous solutions, augmented significantly antibody production, whereas administration of BSA alone or BSA admixed with tuftsin had no immunogenic effect. Studies conducted to elucidate the mechanisms underlying the activation of the immunogenic function of macrophages by the peptide revealed that treatment of cells with antigen and tuftsin increases secretion of interleukin-1 and expression of cell surface Ia encoded antigens. The effect of tuftsin on increasing the immunogenic capacity of antigens may at least partly be attributed to these effects.

Adjuvants, Immunologic↗

PubMed1986

Tuftsin analogues: synthesis, structure-function relationships, and implications for specificity of tuftsin's bioactivity.

Thirteen analogues of the natural macrophage activator peptide tuftsin, ten of which are novel, were synthesized with the aim of exploring the relation between their biological potency and their capacity to attach specifically to cellular tuftsin's receptors. The analogues representing modifications and chain extensions at various parts of the parent tuftsin molecule can be classified as N-terminal analogues, C-terminal analogues, "within-chain" derivatives, or dimers of tuftsin and retrotuftsin. The various synthetic routes employed to prepare the analogues are described. A direct correlation was found between the ability of analogues to inhibit [3H-Arg4]tuftsin specific binding to mice peritoneal macrophages and their capacity to enhance phagocytosis or to inhibit tuftsin-mediated phagocytosis by the cells and to potentiate the cell's immune response.

Animals↗

PubMedDate not supplied

The analgesic activity of some tuftsin- and tuftsin inhibitor-like fragments of the viral coat proteins.

Antinociceptive activity of seven pentapeptide fragments of human adenovirus type 2 (Ad2) virion proteins: Thr-Val-Pro-Pro-Arg (1), Thr-Arg-Pro-Pro-Arg (2), Thr-Gly-Pro-Pro-Thr (3), Pro-Arg-Pro-Pro-Thr (4), Phe-Val-Pro-Pro-Arg (5), Ala-Arg-Pro-Pro-Ala (6), Tyr-Gly-Pro-Pro-Lys (7)--analogs of known tuftsin inhibitor Thr-Lys-Pro-Pro-Arg, was measured by hot-plate procedure. Also two tuftsin-like fragments of epitopes of HIV-1 and HIV-2: Thr-Lys-Ala-Lys (8), Thr-Lys-Glu-Lys (9), and tuftsin analog Thr-Lys-Asp-Lys (10) were tested. In the control experiments the effects of tuftsin and pentapeptide tuftsin inhibitor were also studied. The peptides 2, 4 and 5 were found to produce very strong analgesia after the icv injection. It was observed that pretreatment with peptide 8 remarkably diminished the antinociceptive effect induced by tuftsin.

Adenoviruses, Human↗

PubMed2006

Synthesis of analogues of anthraquinones linked to tuftsin or retro-tuftsin residues as potential topoisomerase inhibitors.

A novel group of [(4-, 5- or 8)-hydroxy-9,10-anthraquinone-1-yl]-(tuftsin or retro-tuftsin) acids and methyl esters has been synthesized as potential anticancer compounds. The corresponding protected tuftsin or retro-tuftsin derivatives were also synthesized. We hope that combining compounds of different mechanisms of action will improve their clinical properties, and that our new analogues will be much more effective against multidrug-resistant tumour cell lines.

Anthraquinones↗

PubMed1981

Tuftsin and D-Arg3-tuftsin possess analgesic action.

Tuftsin has marked analgesic activity but is less potent than D-Arg3-tuftsin. The absence of an antagonistic effect of naloxone on tuftsin and its analogue suggests that these substances do not act on opiate receptors. Tuftsin and its analogues may represent a new class of substances of interest in the search for new analgesics.

Analgesics↗

PubMed1991

Synthesis of glycosylated tuftsins and tuftsin-containing IgG fragment undecapeptide.

Syntheses are described of two new tuftsin derivatives containing a 2-acetamido-2-deoxy-D-galactopyranosyl unit alpha- or beta-glycosidically linked to the threonine's hydroxy side chain function and of the glycosylated undecapeptide corresponding to the tuftsin region of the heavy chain of IgG (amino acid sequence 289-299). The glycosylated tuftsins were synthesized by the solution procedure. Fmoc-[Gal NAc(Ac)3 alpha]Thr-OH and Fmoc-[GalNAc(Ac)3 beta]Thr-OH were allowed to react with H-Lys(Z)-Pro-Arg(NO2)-OBzl by the mixed anhydride procedure and the resulting glycosylated tetrapeptides were fully deblocked by catalytic hydrogenation followed by treatment with potassium cyanide, purified by ion exchange chromatography and characterized by analytical HPLC, elemental and amino acid analyses, optical rotation, and proton NMR spectroscopy. Synthesis of the glycosylated undecapeptide was achieved by the continuous flow solid phase procedure on 4-hydroxymethylphenoxyacetyl-norleucyl derivatized Kieselguhr-supported resin. Fmoc-amino acid symmetrical anhydrides or pentafluorophenyl esters, in the presence of N-hydroxybenzotriazole, were used as the acylating agents. To mimic the native sequence of the tuftsin region at the Fc-domain of immunoglobulin G a 2-acetamido-2-deoxy-beta-D-glucopyranosyl unit was N-glycosidically linked to the amide side chain of Asn 297. The glycosylated asparagine residue was introduced as N2-fluorenylmethyloxycarbonyl-N4-(2-acetamido-3,4,6-tri-O-acetyl-2 -deoxy-beta-D - glucopyranosyl)-asparagine pentafluorophenyl ester. After cleavage from the resin the glycopeptide was deprotected, purified by ion exchange chromatography, and characterized by analytical HPLC, amino acid analysis, high voltage electrophoresis, and proton NMR. The conformational features of the glyco-undecapeptide were determined by circular dichroism measurements both in water and in 98% trifluoroethanol. Results of biological assays will be published elsewhere.

Acylation↗

PubMed1978

Synthesis and biological activity of tuftsin and of [O = C Thr1]-tuftsin. A novel synthetic route to peptides containing N-terminal L -O = C Thr and L - O = C Ser residues.

The cyclization, under alkaline conditions, of N-benzyloxycarbonyl-L-threonine and of N-benzyloxycarbonyl-L-serine to produce 5-methyl-2-oxo-oxazolidine-4-carboxylic acid (O = C Thr1 and 2-oxo-oxazolidine-4-carboxylic acid (O = C Ser), respectively, was investigated and found to be efficient and racemization-free. Similar was the cyclization which accompanied the basic hydrolysis of N-benzyl-oxycarbonyl-L-threonyl-L-phenylalanine methyl ester and of N-benzyloxy-carbonyl-L-seryl-DL-valine ethyl ester, and which resulted in the formation of L - O = C Thr-L-Phe and L - O = C Ser-DL-Val, respectively. The reaction was applied to the synthesis of [O = C Thr1] tuftsin, an active analog of the phagocytosis stimulating peptide tuftsin. A new synthetic route to tuftsin is also described.

Amino Acid Sequence↗

PubMed1995

Simulations of conformers of tuftsin and a cyclic tuftsin analog.

The conformational properties of the configurational isomers of tuftsin, a linear tetrapeptide with the sequence Thr-Lys-Pro-Arg, were investigated with six 1 ns molecular dynamics simulations in explicit water and in a 1.0 m NaCl solution. The average conformation of the cis isomer is a type VI beta-turn. Our results indicate that water-peptide hydrogen bonding, in addition to intramolecular hydrogen bonds, stabilizes the cis conformer. The trans isomer is neither a beta- nor a gamma-turn. Results are compared with parallel studies on a cyclic analog of tuftsin, cyclo(Thr-Lys-Pro-Arg-Gly). The addition of salt does, not influence the backbone conformation of the peptide. Differences between the structures are confined to the side-chain orientations of the Lys and Arg residues.

Amino Acid Sequence↗

PubMed1977

Tuftsin and some analogs: synthesis and interaction with human polymorphonuclear leukocytes.

The phagocytosis-stimulating tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, was synthesized by both conventional and polymeric-reagent approaches. Using a combination of the two methods several analogs were prepared, including: [Ala1]tuftsin, [Lys1]tuftsin, [Ser1]tuftsin, [Val1]tuftsin, acetyl-tuftsin, p-aminophenylacetyl-tuftsin and tyrosyl-tuftsin. [Des-Thr1]tuftsin and [omega-NO2(4)]tuftsin were synthesized using a conventional procedure. The effects of synthetic peptides on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes were investigated. Tuftsin and to a lesser extent [Lys1]tuftsin and [Ser1]tuftsin were found to stimulate phagocytosis, whereas the other analogs synthesized as well as [Ser1]tuftsin exhibited inhibitory effects to tuftsin's action. Tuftsin alone has stimulated nitroblue tetrazolium reduction; [Des-Thr1]tuftsin and [Ala1]tuftsin repressed this stimulation, while the other peptides showed no effect.

Hexosephosphates↗

PubMed1986

In vivo immunopharmacological properties of tuftsin (Thr-Lys-Pro-Arg) and some analogues.

Tuftsin (Thr-Lys-Pro-Arg) is part of the Fc fragment of a leukophilic IgG and is a stimulator of the phagocytic activity of macrophages and polymorphonuclear cells (PMN) when cleaved from its carrier molecule. Tuftsin was shown to stimulate in vitro all PMN and macrophage functions examined through binding to specific cell surface receptors. In the present work, we provide further evidence that synthetic tuftsin administered to mice may act as an immunomodulator and that its effects on immune functions may result from a primary action on macrophages. After i.v. injection at a dosage of 25 micrograms/mouse, tuftsin stimulated effector (phagocytosis) and regulatory (IL1 production) functions of macrophages and potentiated DTH reaction. Lymphocyte functions (proliferative response to mitogens, T cell-mediated cytotoxicity, IL2 and gamma IFN production) were depressed at times at which macrophage activities were maximally enhanced, suggesting that negative regulatory functions of these latter cells were also stimulated. Tuftsin analogues were synthetized representing substitution or derivatization of the threonyl residue. The relative potencies of these analogues in augmenting phagocytosis-induced chemiluminescence of macrophages were tuftsin greater than or equal to (Gly1)-tuftsin greater than for-tuftsin greater than (for-Met1)-tuftsin greater than (Met1)-tuftsin. Concerning potentiation of DTH reaction the order was (Gly1)-tuftsin greater than or equal to (for-Met1)tuftsin greater than tuftsin greater than (Met1)-tuftsin greater than for-tuftsin. In contrast to tuftsin, none of the analogues induced depression of spleen cell reactivity to mitogens. In addition, (for Met1)-tuftsin administration resulted in an increased production of IL2 and IFN by ConA-stimulated spleen cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

PubMed2006

Safety, efficacy and pharmacokinetics of tuftsin-loaded nystatin liposomes in murine model.

Present study was performed to evaluate the efficacy, toxicity and pharmacokinetics of antifungal drug nystatin incorporated in immunomodulator tuftsin-bearing liposomes. In vitro toxicity of free nystatin and nystatin incorporated in tuftsin-free or tuftsin-loaded liposomes was assessed by incubation of nystatin formulations with human erythrocytes. The toxicity profile of free nystatin and liposomal formulations of nystatin with or without tuftsin was also analyzed by monitoring the level of blood urea nitrogen (BUN) and serum creatinine in the treated BALB/c mice. The results of the present work showed that tuftsin-loaded nystatin liposomes like conventional nystatin liposomes exerted less toxicity to human erythrocytes as compared with free nystatin. Moreover, mice treated with tuftsin-loaded nystatin liposomes showed insignificant elevation in the biochemical values of serum creatinine and blood urea. The stability of nystatin liposomes upon incorporation of tuftsin was evaluated by monitoring the leakage of the entrapped drug in human serum. Tuftsin-loaded liposomes held nystatin for longer duration in the presence of serum than identical nystatin liposomes without tuftsin. Pharmacokinetics of the both tuftsin-free or tuftsin-loaded liposomal formulations nystatin was analyzed by determining the level of nystatin in the systemic circulation of mice at different time points. Mice injected with tuftsin-loaded nystatin liposomes showed higher level of the drug in the systemic circulation compared with those treated with conventional nystatin liposomes. The efficacy of tuftsin-loaded nystatin liposomes against A. fumigatus was evaluated by assessing the fungal burden in the lungs of treated mice. Treatment with tuftsin-loaded nystatin liposomes was most effective in eliminating fungal burden from lung tissues of infected mice compared to those treated with free nystatin or nystatin liposomes without tuftsin. The immunopotentiating activity, increased stability and less toxicity of tuftsin-incorporated nystatin liposomes, supports the idea for its prophylactic and therapeutic use in the clinical setting.

Animals↗

PubMed1979

Tuftsin-macrophage interaction: specific binding and augmentation of phagocytosis.

The binding of [3H]tuftsin to normal and in vivo stimulated mouse peritoneal macrophage populations was studied at 22 degrees C. The [3H]tuftsin binding to thioglycollate-stimulated macrophages was shown to be rapid and saturable, with an equilibrium dissociation constant (K(D)) (calculated from a Scatchard plot) of 5.3 X 10(-8) M. The calculated number of binding sites per macrophage amounts to approximately 72,000. Binding competition studies with unlabelled tuftsin yielded a K(D) of 5.0 X 10(-8) M. [3H] [N-Acetyl-Thr1]tuftsin, an inactive analog of tuftsin, failed to bind specifically to thioglycollate-stimulated macrophages. [N-Acetyl-Thr1]tuftsin and the tripeptide [Des-Arg4]tuftsin failed to compete for tuftsin binding sites, while [D-Arg4]tuftsin, an analog with small tuftsin-like activity, exhibited a low degree of inhibition of [3H]tuftsin binding. Thus a rather high degree of specificity is involved in the binding of the tetrapeptide. Normal as well as six different macrophage populations induced by stimulation with thioglycollate, concanavalin-A, starch, mineral oil, glucan and Bacillus Calmette Guerrin (BCG), exhibited a similar degree of binding of [3H]tuftsin. Corynebacterium parvum (CP)-stimulated macrophages, on the other hand, showed a 6- to 10-fold-lower capacity for tuftsin binding. Under similar experimental conditions, mouse fibroblast and lymphocyte preparations revealed no detectable specific binding. Tuftsin augmented the phagocytic response of normal and stimulated macrophages assessed both for phagocytosis mediated via the Fc-receptor and via non-specific receptors. CP-stimulated macrophages did not exhibit an increased phagocytic response upon treatment with tuftsin.

Animals↗

PubMed1996

1-Aminocyclobutanecarboxylic acid derivatives as novel structural elements in bioactive peptides: application to tuftsin analogs.

Four novel 2,4-methano amino acids (MAAs, 1-aminocyclobutane-1-carboxylic acids) were synthesized. These include the basic MAA analogs of lysine (16), ornithine (5), and arginine (6) and the neutral methanovaline (22), related to proline. The above MAAs, as well as the MAA analog of homothreonine (7), were incorporated into the peptide chain of the immunomodulatory peptide tuftsin, Thr-Lys-Pro-Arg, known to enhance several biological activities mediated by phagocytic cells. The synthetic methano tuftsin analogs were assayed for their ability to stimulate interleukin-6 (IL-6) secretion by mouse peritoneal macrophages and for their stability in human serum toward enzymatic degradation. It was found that, at 2 x 10(-7) M, [MThr1]tuftsin (24) and an isomer of [MVal3]tuftsin (27a) were considerably more active than the parent peptide in augmentation of cytokine release. [MOrn2]Tuftsin (25) was equally potent. The analogs [MThr1]tuftsin (24) and [MOrn2]tuftsin (25), both pertaining to the proteolytically sensitive Thr-Lys bond of tuftsin, exhibited high resistance to enzymatic hydrolysis as compared to tuftsin. Using specific rabbit anti-tuftsin antibodies in a competitive enzyme-linked immunosorbent assay (ELISA) revealed that none of the MAA analogs can cross-react with tuftsin. It may indicate that the peptides assume global structures different than that of tuftsin.

Amino Acids↗

PubMed2005

Incorporation of amphotericin B in tuftsin-bearing liposomes showed enhanced efficacy against systemic cryptococcosis in leucopenic mice.

OBJECTIVES: The role of the immunomodulator tuftsin in enhancing the antifungal activity of liposomal amphotericin B against Cryptococcus neoformans in leucopenic mice was assessed. METHODS: In the present study, we investigated the antifungal activity of amphotericin B liposomes with tuftsin grafted on the surface. Mice were treated with free amphotericin B as well as liposomal formulations after C. neoformans infection. For prophylactic studies, mice were pre-treated with liposomal tuftsin (50 microg/mL) for three consecutive days prior to C. neoformans infection (7 x 10(5) cfu/mouse). Chemotherapy, with tuftsin-free and tuftsin-bearing amphotericin B liposomes, was started 24 h post C. neoformans infection. The role of tuftsin in immunoaugmentative therapy was assessed by survival and cfu of treated mice. RESULTS: Amphotericin B entrapped in tuftsin-bearing liposomes showed increased anticryptococcal activity in the murine model. Moreover, tuftsin pre-treatment further augmented the antifungal activity of liposomal amphotericin B in leucopenic mice. Incorporation of tuftsin in liposomes resulted in increased anticryptococcal activity of liposomal amphotericin B compared with amphotericin B deoxycholate and conventional liposomal amphotericin B formulations. CONCLUSIONS: The enhanced anticryptococcal activity of amphotericin B in tuftsin-liposomes can be attributed to the immune-stimulating property of tuftsin. Tuftsin activates the key immune cells, due to the presence of its receptors on macrophages and neutrophils, for a better fight against pathogens. Simultaneous liposome-mediated delivery of amphotericin B to the site of infection kills the pathogens more effectively.

Amphotericin B↗

PubMed2006

Toxicity, stability and pharmacokinetics of amphotericin B in immunomodulator tuftsin-bearing liposomes in a murine model.

OBJECTIVES: In the present study we evaluated the pharmacokinetics and toxicity of amphotericin B in immunomodulator tuftsin-loaded liposomes in a murine model. METHODS: Stability of amphotericin B liposomes was tested by incubating one volume of liposomal formulations of amphotericin B with nine volumes of serum. The pharmacokinetics of amphotericin B in Candida albicans-infected mice treated with conventional and tuftsin-loaded amphotericin B liposomes was evaluated over a period of 24 h. In vitro toxicity of amphotericin B deoxycholate, as well as amphotericin B liposomes, was tested by incubation with human erythrocytes for 1 h at 37 degrees C. To assess amphotericin B-induced in vivo toxicity, BALB/c mice were injected with three doses of amphotericin B deoxycholate, as well as amphotericin B liposomal formulations on days 1, 2 and 3 post C. albicans infection. Blood from treated mice was taken by retro-orbital puncture to test renal function parameters such as serum creatinine and urea. RESULTS: In vitro stability studies revealed that tuftsin-bearing amphotericin B liposomes released only 11% of the total liposomal amphotericin B in the serum, while it was found to be 19% from identical tuftsin-free amphotericin B liposomes. Both tuftsin-loaded as well as tuftsin-free liposomal formulations of amphotericin B induced approximately 20% haemolysis of erythrocytes at a dose of 40 mg/L, while the same amount of drug in amphotericin B deoxycholate caused 100% lysis of the erythrocytes. Pharmacokinetic studies revealed that subsequent to administration of various formulations of amphotericin B, there was 32 mg/L amphotericin B in the systemic circulation of mice treated with tuftsin-bearing amphotericin B liposomes, while it was 25 mg/L for amphotericin B liposomes, 4 h post drug administration. In vivo toxicity studies demonstrated that the amphotericin B deoxycholate formulation induced elevations in serum creatinine (approximately 300% of control) and blood urea (approximately 380% of control) values, while these values were substantially less (blood urea approximately 150% of control and serum creatinine approximately 210% of control) in the animals treated with the tuftsin-loaded amphotericin B liposomal formulation. Further, the administration of amphotericin B deoxycholate (1 mg/kg) in BALB/c mice at a dose of 1 mg/kg body weight led to the accumulation of 18.6 +/- 5.25 g/kg (of amphotericin B) in kidneys. On the other hand, administration of liposomal amphotericin B and tuftsin-bearing liposomal amphotericin B at a dose of 5 mg/kg body weight resulted in accumulation of 8.8 +/- 2.0 and 4.0 +/- 1.6 g/kg of amphotericin B, respectively, in the kidneys of treated animals. CONCLUSIONS: Co-administration of immunomodulator tuftsin along with liposomal formulations of amphotericin B successfully minimizes toxicity, as well as other side effects of the drug. Interestingly, tuftsin also increased the stability of liposomal amphotericin B. Superior efficacy, reliable safety and favourable pharmacodynamics of tuftsin-loaded amphotericin B liposomes suggest their potential therapeutic value in the management of fungal infections.

Amphotericin B↗

PubMed1994

Stimulation of phagocytic activity of murine Kupffer cells by tuftsin.

Tuftsin (Thr-Lys-Pro-Arg) is a natural immunomodulating peptide. We have investigated for the presence of a specific tuftsin receptor on murine Kupffer cells using fluorescein-labeled tuftsin, which retains full biological activity. After incubation with fluorescein-labeled tuftsin, Kupffer cells displayed clear binding of this compound on the plasma membrane. Excess tuftsin inhibited this binding, indicating the presence of specific tuftsin receptors on the Kupffer cells. We then investigated the effect of tuftsin on the phagocytic activity of these cells. Phagocytosis assays were performed on 24-well plates between murine Kupffer cells and fluorescent microspheres. The greatest stimulatory effect of tuftsin on percent phagocytic cells over the control value was observed when the cells were incubated with particles at 1 microgram/ml tuftsin for 15 min at 37 degrees C with a particle-to-Kupffer cell ratio of 50:1. Tuftsin also markedly increased the number of particles engulfed by Kupffer cells under the same conditions. These results indicate that Kupffer cells have specific tuftsin receptors; thus tuftsin can stimulate phagocytic activity of Kupffer cells, which constitute the majority of macrophages in the host and are situated strategically in the liver for host defense.

Amino Acid Sequence↗