Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tuftsin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1990

Tuftsin-enhanced thymidine incorporation by murine splenic monocytes.

Tuftsin (Thr-Lys-Pro-Arg), a natural immunomodulating peptide originally found to stimulate phagocytosis by polymorphonuclear leukocytes (PMN), is now known to bind to both PMN and monocyte-macrophages, affecting many of their functions. Administration of tuftsin induces leukocytosis in vivo. We have recently observed that while tuftsin remains in the cytoplasm upon binding and internalization in human PMNs, it translocates into the human monocyte nucleus, suggesting that tuftsin may directly affect growth of monocytes. We have therefore examined the effect of tuftsin on [3H]thymidine incorporation in fractions of murine splenocytes to identify a cell population responding to tuftsin. Tuftsin showed the greatest effect in [3H]thymidine incorporation of splenocytes over controls at optimum conditions of 2% fetal bovine serum and 1 microgram/ml of tuftsin. Splenocyte fractionation by Lymphocyte Separation Medium indicated that tuftsin primarily affects the mononuclear cell fraction; further fractionation revealed that tuftsin affects mostly the monocytes that adhered to plastic. We subsequently further purified the splenic monocytes by repeated plastic adhesion and Percoll gradient separation, to show that tuftsin increases [3H]thymidine incorporation of these highly purified monocytes.

Amino Acid Sequence↗
PubMed1981

Tuftsin: a naturally occurring immunopotentiating factor. I. In vitro enhancement of murine natural cell-mediated cytotoxicity.

Tuftsin is a physiologic tetrapeptide, which has recently been shown to possess immunoadjuvant properties including the stimulation of macrophage and granulocyte phagocytosis, migration, bactericidal, and tumoricidal activities. Tuftsin has also been reported to possess in vivo immunologically mediated anti-tumor potential. To determine the potential role of tuftsin as an antineoplastic immunoadjuvant, the in vitro effects of tuftsin on murine natural cell-mediated cytotoxicity were studied. We observed that in vitro treatment of mouse splenic effector cells with synthetic tuftsin induced a pronounced enhancement of natural killer cell (NKC) cytotoxicity against the T cell lymphoma Yac-1. The magnitude of NKC enhancement was directly dependent upon the concentration of tuftsin employed, with maximum NKC stimulation observed at tuftsin concentrations of 50 to 100 microgram/ml. The tuftsin induced enhancement of NKC activity was not strain specific, since equivalent stimulation was seen in CBA/J, C56BL/10, and DBA/2 mice. Elimination of macrophages, monocytes, T cells, and immunoglobulin-bearing cells had no effect on the dose-dependent tuftsin stimulation of natural cell-mediated cytotoxicity; thus the characteristics of the effector cells activated by tuftsin were consistent with those reported for NKC. We also observed that treatment of splenic effector cells with tuftsin prolonged the cytotoxic capabilities of these cells beyond 18 hr.

Adjuvants, Immunologic↗
PubMed1984

Receptor-mediated endocytosis of tuftsin by macrophage cells.

A fluorescent analog of the phagocytosis stimulating peptide tuftsin was prepared by coupling tetramethyl rhodamine isothiocyanate to a C-terminal elongated derivative of tuftsin. This analog, Thr-Lys-Pro-Arg-Gly-Lys(N epsilon-tetramethyl rhodamine)-OH, was used to visualize tuftsin receptors on mice macrophage cells by fluorescent image intensification. Fluorescent labelling was carried out at 37 degrees C, using a concentration of 200 nM and 2 microM of the fluorescent tuftsin derivative. The formation of peptide-receptor clusters and their subsequent internalization, as discerned by image intensification, were rapid processes, 5 min and 5-30 min, respectively. Preincubation of macrophages with tuftsin for various time intervals, followed by quantification of the tuftsin receptor using radiolabelled tuftsin, suggest that tuftsin receptors are initially increased in amount (5-7 min) and subsequently reduced (after 10-15 min) as judged by sites available for tritiated tuftsin. The binding studies are rather complementary to the fluorescence observations and support the assumption that the tuftsin receptor on the membrane of the mice macrophage cell is rapidly mobilized.

Animals↗
PubMed1981

Inactivation of phagocytosis-stimulating activity of tuftsin by polymorphonuclear neutrophils. A possible role of leucine aminopeptidase as an ecto-enzyme.

The subcellular localization of the tuftsin-inactivating activity was studied using guinea-pig polymorphonuclear neutrophils and the following results were obtained. 1. The tuftsin-inactivating activity was present in the membrane fraction but not in the cytosol and the granular fractions. 2. Intact neutrophils inactivated tuftsin rapidly. However, when neutrophils were modified chemically by a poorly permeant reagent, diazotized sulfanilic acid, the tuftsin-inactivating activity decreased significantly without any inhibition of marker enzymes of cytosol, microsome, granules and mitochondria, suggesting that the tuftsin-inactivating activity is located on the plasma membrane as an ecto-enzyme. 3. When neutrophils were modified by diazotized sulfanilic acid at different concentrations, the tuftsin-inactivating activity of neutrophils was inhibited in proportion to the degree of inhibition of the activity of leucine aminopeptidase, an ecto-enzyme. 4, Hydrolysis of L-leucyl-beta-naphthylamide, a synthetic substrate of leucine aminopeptidase, was inhibited competitively by tuftsin. 5. Treatment of neutrophils with serine protease inhibitors affected neither tuftsin-inactivating nor leucine aminopeptidase activity at all, indicating no involvement of serine proteases, which is said to be located on the cell surface membrane, in the tuftsin-inactivation activity of neutrophils. The possibility was deduced from the above results that leucine aminopeptidase may act as a tuftsin-inactivating enzyme.

Animals↗
PubMed2002

Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome.

BACKGROUND: Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. METHODS: Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. RESULTS: Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). COMMENT: Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.

Adult↗
PubMed1991

The generation of antibody in mice to tuftsin: a naturally occurring phagocytosis stimulating tetrapeptide.

Tuftsin (Thr-Lys-Pro-Arg) is a naturally occurring tetrapeptide that stimulates most known functions of the polymorphonuclear leukocyte and macrophage cell lines. We previously reported our unsuccessful attempts to generate antituftsin antibodies by conjugating tuftsin to several carrier proteins and by polymerizing the peptide with glutaraldehyde. To render tuftsin antigenic the following modifications were made to native tuftsin: three glycine residues were added to the N terminus of tuftsin (Gly3-tuf) and cysteine was added to the N terminus (Cys-tuf) and to the C terminus (tuf-Cys). Native tuftsin was covalently conjugated to sheep red blood cells (SRBC). In a separate experiment Balb/c mice primed with SRBC were immunized with 10(7) SRBC peptide conjugate. Native tuftsin and Gly3-tuf were also conjugated to keyhole limpet hemocyanin (KLH). In another experiment KLH and cationized bovine serum albumin (cBSA) were activated with sulfo-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (s-SMCC), which was used to control orientation of tuf-Cys and Cys-tuf when conjugated to each carrier protein. All conjugates were administered in complete Freund's adjuvant (CFA) except for cBSA conjugates which were administered in alum. Antibody response was determined by solid phase radioimmunoassay. Results showed that specific antituftsin antibodies were elicited only by Cys-tuf, conjugated to KLH. This study reaffirms that tuftsin is weakly antigenic and confirms the previous work by Gottlieb et al. that antibody to tuftsin can only be elicited when tuftsin is conjugated to the carrier protein KLH in a manner that leaves the peptide carboxyl end free.

Amino Acid Sequence↗
PubMedDate not supplied

The effect of anti-tuftsin antibody on the phagocytosis of bacteria by human neutrophils.

Tuftsin (Thr-Lys-Pro-Arg) is a naturally occurring tetrapeptide which stimulates most known functions of the polymorphonuclear and mononuclear phagocytic cell lines. Although tuftsin is a well characterized bioactive peptide, the exact physiological role tuftsin plays remains unclear. Specific mouse anti-tuftsin antiserum generated in our laboratory, is now available for phagocytosis inhibition studies. Monolayers of human neutrophils were prepared on glass coverslips from a few drops of finger prick blood obtained from a single healthy donor. The monolayers were treated with and without mouse anti-tuftsin antiserum at dilutions of 1:1000 or 1:2000. Exogenous tuftsin (1 microgram/ml) was also added with and without antibody. Treated and untreated neutrophils were subsequently incubated with unopsonized Staphylococcus aureus. The proportion of cells accomplishing phagocytosis (phagocytic index) and the number of bacteria engulfed per cell (avidity index) were recorded. The results showed that exogenous tuftsin increased phagocytosis while the addition of mouse anti-tuftsin antiserum at a 1:1000 dilution inhibited phagocytosis both with and without exogenous tuftsin. This effect was diminished by the antiserum at the 1:2000 dilution. This study reaffirms that tuftsin plays an important physiological role in phagocytosis.

Amino Acid Sequence↗
PubMed1981

Tuftsin, Thr-Lys-Pro-Arg. Anatomy of an immunologically active peptide.

Tuftsin, a natural occurring tetrapeptide, has been found to exhibit several biological activities connected with immune system function. Although little is known about tuftsin's 'biogenesis', much information has been gleaned about its structure-function relationships, which have shown that several features of the molecule are essential for expression of full biological activity. Furthermore, specific receptor sites for tuftsin have been found to exist exclusively on phagocytic cells. Research indicates that tuftsin binding to target cells effect intracellular calcium and cyclic nucleotide levels. Implication of these facts on tuftsin's mode of action are discussed. Basic peptidic segments resembling tuftsin are found in a variety of regulatory peptides. Questions are, therefore, raised as to the biospecificity an cross-reactivity of these sequences. Substance P, one such peptide, which binds with and activates tuftsin receptors, is described. In light of tuftsin's therapeutic potential, assays for its determination have been introduced. When applied to analyze human blood serum of normal as well as of various pathological origins, direct correlation was found between tuftsin levels and susceptibility to bacterial infections.

Amino Acid Sequence↗
PubMed1994

Studies of human granulocyte phagocytosis stimulation by tuftsin.

Tuftsin (Thr-Lys-Pro-Arg), a natural immunomodulating peptide originally found to stimulate phagocytosis by polymorphonuclear leukocytes (PMNs), is now known to bind to both PMNs and monocyte-macrophages, affecting their phagocytosis and other functions. The potential roles of tuftsin in surgery-related infections have been documented using animal models. However, there have been some difficulties in demonstrating the phagocytosis-stimulating activity of tuftsin. In view of this, we have developed a suitable human PMN phagocytosis assay for tuftsin and performed preliminary kinetic studies. The assay was performed on 24-well plates between PMNs and fluorescent microspheres. The greatest effect of tuftsin over the control was observed under the following conditions: 15 min incubation at 37 degrees C with 5 micrograms/ml tuftsin and a 50:1 ratio of particle to PMN. Particles bound on the surface of PMNs were removed by washing and trypsin treatment, followed by centrifugation through fetal bovine serum. This allowed us to utilize flow cytometry in this study. A flow cytometric procedure was then successfully adapted to human PMN phagocytosis that established a high correlation between microscopic evaluation and flow cytometry of phagocytosis. In addition to the above determinations of the percentage of phagocytic cells, we evaluated the effect of tuftsin on the number of particles engulfed by PMNs. Under the above optimum conditions, tuftsin has greater impact on the number of particles engulfed than on the percentage of phagocytic cells.

Amino Acid Sequence↗
PubMedDate not supplied

Synthesis and biological activity of [L-3,4-dehydroproline3]-tuftsin.

A 3,4-dehydroproline analogue of tuftsin (L-Thr-L-Lys-L-Pro-L-Arg) was prepared by the solid phase synthetic method. Following reversed-phase high performance liquid chromatography (HPLC) purification, the analogue was compared to tuftsin for its ability to to enhance the chemotactic, bactericidal and phagocytic activities of polymorphonuclear leukocytes (PMN). Both tuftsin and [delta 3-pro3]- tuftsin elicited a similar significant chemotactic effect at a concentration of 10 micrograms/ml. A slight suppression of the chemotactic activity was observed with tuftsin at 10(-3) micrograms/ml and with [delta 3-pro3]-tuftsin at concentrations of 10(-3), 10(-2) (significant) and 10-1 micrograms/ml. Although similar bactericidal activities were observed for both peptides, PMN exposed to [delta 3-pro 3]-tuftsin exhibited increased phagocytic indicies 2-4 times that of tuftsin-treated PMN at concentrations of 0.4, 0.6 and 1.0 microgram/ml.

Amino Acids↗
PubMed1999

Tuftsin: on the 30-year anniversary of Victor Najjar's discovery.

After a short description of the results of Victor Najjar's research on tuftsin and of the discoveries done by other authors in the early stage of tuftsin investigation, the current state of work on tuftsin is presented, based mainly on the literature published in the years 1984-1997. The presentation follows this order: the occurrence of tuftsin and retro-tuftsin sequences in proteins, their synthesis and biology, the antigenic properties of tuftsin, its influence on phagocytic cells, and other biologic activities of tuftsin, including antimicrobial, antiviral, antitumor and central effects, and the search for tuftsin superactive analogs.

Amino Acid Sequence↗
PubMed2002

Superior chemotherapeutic efficacy of amphotericin B in tuftsin-bearing liposomes against Leishmania donovani infection in hamsters.

Chemotherapeutic efficacy of the amphotericin B (Amp B), which is the drug of choice for treatment of the leishmanial infections (kala-azar) that become resistant to the conventional chemotherapy using antimonials, has been examined in the Leishmania donovani infected hamsters after encapsulating the drug in tuftsin-free as well as tuftsin-bearing liposomes. The activity was significantly increased (p < 0.05) by delivering Amp B in tuftsin-free liposomes. This antileishmanial effect of the liposomized Amp B was further increased (p < 0.05) by grafting the natural macrophage-activator tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), on the liposome's surface. This could possibly be attributed to both the enhanced drug tolerance after liposomization as well as to the increased uptake of tuftsin-bearing Amp B-laden liposomes by the macrophages. In addition to the increased efficacy, encapsulation of Amp B in the tuftsin-bearing liposomes also enhanced the drug accessibility to areas (e.g. bone marrow) that are otherwise inaccessible to the free drug. These results further demonstrate the usefulness of tuftsin-bearing liposomes as drug vehicles in treatment of the macrophage-based infections that have been reviewed recently (Agrawal, A.K. and Gupta, C.M. (2000). Tuftsin-bearing liposomes in treatment of macrophage-based infections, Adv. Drug Deliv. Rev., 41, 135-146).

Amphotericin B↗
PubMed1991

Enzyme immunoassay of phagocytosis stimulating tetrapeptide "tuftsin" in normal and leprosy sera.

The serum concentrations of the phagocytosis stimulating the tetrapeptide, tuftsin, were determined by competitive enzyme immunoassay in borderline tuberculoid/tuberculoid (BT/TT, 16 cases), borderline lepromatous/lepromatous (BL/LL, 16 cases), and in healthy controls (20 cases). Using checkerboard titration, 10 ng/well of diphtheria toxoid-p-aminophenylacetyl tuftsin (DTPT) conjugate when incubated with tuftsin antisera at 1:15,000 dilution with a preincubation time of 60 min with the competitor (tuftsin) followed by a further 60-min incubation onto the DTPT-coated wells gave consistent results with a sensitivity of 5 ng/well tuftsin. The mean serum tuftsin concentration was significantly lower in BL/LL patients (134.42 +/- 48.7 ng/ml, p less than 0.01) than in healthy controls (262.86 +/- 59.8 ng/ml), while BT/TT sera (210.94 +/- 75.5 ng/ml) showed slightly decreased levels than did normals, which was not statistically significant. The mean serum IgG levels in BL/LL and BT/TT patients (37.26 +/- 10.99 mg/ml; 28.08 +/- 6.57 mg/ml, respectively) showed significantly (p less than 0.001) higher concentrations than did healthy controls (12.3 +/- 3.6 mg/ml). These observations on the serum concentrations of tuftsin and IgG in leprosy individuals suggest that there is splenic dysfunction in BL/LL patients in terms of the processing of leukokinin to release the free, active molecule tuftsin.

Binding, Competitive↗
PubMedDate not supplied

Potential use of tuftsin in treatment of candida peritonitis in a murine model.

A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis caused by Candida albicans. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. Tuftsin was found to increase thioglycollate-elicited mouse peritoneal macrophage activity. 2x10(-7) M tuftsin enhanced two-fold cell association with radiolabelled candida, superoxide aniom production, and killing activity. Thus, a model consisting of mice undergoing peritoneal dialysis was developed in order to study the use of tuftsin as a therapeutic drug against peritoneal candidiasis. Administration of tuftsin (50 micrograms/mouse) before candidiasis induction with a lethal dose of candida (7x10(8) candida per mouse) improved mouse survival up to 70%, compared with 10% in the control group. The potential of tuftsin as a treatment for candidiasis was shown when the infection was induced with a sublethal dose of candida. Daily intraperitoneal injections of tuftsin (50 micrograms) to the sublethally infected mice caused a significant decrease in the number of candida recovered from the peritoneal cavity and from the blood (from 700 +/- 190 to 110 +/- 26 CFU/ml and from 100 +/- 26 CFU/ml to 17 +/- 8 CFU/ml, respectively). In addition, a larger number of peritoneal macrophages with greater phagocytic and killing activity were found in the tuftsin-treated mice. The effect of tuftsin may promote its potential use in the therapy of peritonitis in patients undergoing chronic peritoneal dialysis.

Animals↗
PubMedDate not supplied

Effect of tuftsin on human Kupffer cell.

BACKGROUND/AIMS: Kupffer cells are the most important category of reticuloendothelial cells which are critical for host defense in the liver. We investigated the effects of tuftsin (Thr-Lys-Pro-Arg) on human Kupffer cells. METHODOLOGY: Human Kupffer cells were obtained from the livers of patients with colon cancer. Phagocytosis assay was done by microscopic counting of the number of Kupffer cells that engulfed fluorescent particle(s), and the number of the particles engulfed per Kupffer cell when Kupffer cells were incubated with and without tuftsin. Effect of tuftsin on the release of tumor necrosis factor from Kupffer cells was also studied. RESULTS: Phagocytosis was enhanced significantly by tuftsin. The greatest effect on percentage of phagocytic cells was observed at 1.0 microg/ml of tuftsin. The mean number of particles engulfed per Kupffer cell was also increased with tuftsin 1.0 microg/ml. Tumor necrosis factor release was also significantly increased; the greatest effect was observed at 1.0 microg/ml of tuftsin. CONCLUSIONS: Tuftsin enhances phagocytic activity and tumor necrosis factor release of human Kupffer cells, which are advantageous for host defense against invading microorganisms and tumor cells.

Cells, Cultured↗
PubMed1983

Peptide fragments from the tuftsin containing domain of immunoglobulin G synthesis and biological activity.

Peptides corresponding to sequences of the Fc-portion of immunoglobulin G (IgG) surrounding and containing the tuftsin molecule were synthesized. The compounds were assayed for their ability to compete with [3H-Arg4]tuftsin in binding to mouse peritoneal macrophages and to stimulate the cell's capacity to phagocytize. Despite the sensitivity that tuftsin has demonstrated to various chemical modifications and structural alterations which usually cause reduction or total loss of biological activity, IgG-related analogs possess potent tuftsin-like activity. The activity is not caused by enzymatic breakdown and release of tuftsin. The fact that the elongated tuftsin analogs can specifically be attached to and activate macrophages may indicate a possible connection between Fc and tuftsin's receptors.

Amino Acid Sequence↗
PubMed1990

Effect of tuftsin stimulation on the microbicidal activity exerted by blood monocyte-macrophages of leprosy patients.

The ability of blood monocyte/macrophages from normal donors, tuberculoid leprosy (BT/TT) and lepromatous leprosy (BL/LL) patients to exert enhanced microbicidal activity was assayed after stimulating with 0.8 microM tuftsin, as a function of the duration of cultures in vitro. Normal and BT/TT macrophage cultures showed a statistically significant increase in microbicidal activity against Staphylococcus aureus at all ages of culture (6 h to 14 days), though the overall magnitude of the enhancement shows a decrease with increasing culture age in the same populations. However, 14-day old BL/LL macrophage cultures were unable to undergo tuftsin-mediated stimulation of microbicidal activity against S. aureus and even, fresh 6 h-old cultures exhibited a tuftsin-stimulated response profile similar to 14-day old normal and BT/TT cultures. Also, 7 and 14-day cultures of normal, BT/TT and BL/LL macrophages were unable to inhibit/kill intracellular Mycobacterium leprae after a single stimulation with 0.8 microM tuftsin. However, serial, daily stimulation with 0.8 microM tuftsin resulted in 77-140% inhibition of 3H-thymidine uptake by the 12th day of cultures in vitro in the three groups. These results suggest that BL/LL macrophages exhibit a premature inability to undergo tuftsin stimulated microbicidal activity, which may possibly be reversed by serial dosage of tuftsin.

Blood Bactericidal Activity↗
PubMed1997

Quantitative assessment of tuftsin receptor expression and second messenger during in vitro differentiation of peripheral blood derived monocytes of leprosy patients.

Tuftsin, a tetrapeptide (Thr-Lys-Pro-Arg) is known to potentiate the immunogenic activity of antigen-fed macrophages. The present study describes the mechanism of action of tuftsin in leprosy patients throughout the spectrum of the disease in vitro as a function of culture age in terms of (A) involvement of second messengers cAMP, cGMP and [Ca2+]i and (B) number of tuftsin binding sites/and their relative affinities on the monocytes/macrophages. There is apparently no direct involvement of either cAMP or cGMP while comparing the stimulated and unstimulated cultures during in vitro differentiation of monocytes (days 1, 3 and 7) or with the spectrum of the disease. Inhibition of superoxide anion release either by verapamil or with Quin 2 clearly demonstrated the involvement of [Ca2+]i as a second messenger during activation of monocytes/macrophages with tuftsin. Scatchard analysis of radiolabelled tuftsin binding data showed only one type of tuftsin receptor (low affinity) on BL/ LL monocytes/macrophages and normal and BT/TT cultures showed a gradual change in receptor number and affinities (low to high) with the maturation of monocytes to macrophages in contrast to BL/LL groups which displayed significantly less number of receptors. This study elicits a model which depicts that the biological responses/metabolic functions of early monocytes of normal and BT/TT gradually increase with the age of the culture till day 3 and tapers off thereafter in the older (day 7) cultures, whereas the monocytes/macrophages of BL/LL group are metabolically active only on day 1. The present study thereby implies that the clearance of leprosy bacilli from lepromatous leprosy lesions as a consequence of local or systemic immunotherapy (in the present study, the macrophage modulation by tuftsin) depends on the influx of new competent macrophages, rather than the local activation of resident lepromatous macrophages.

Calcium↗