Search

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates and remains stable in the fatty tissues and liver of rodents for a long time. Considering the pronounced difference between species, long-term, low dose hepatic effects of TCDD were investigated after subcutaneous administration of TCDD into rhesus monkeys during pregnancy. Macroscopic and histopathological examination of the liver carried out 4 y after TCDD administration demonstrated intrahepatic focal fatty changes, infarction, hemorrhage, microthrombi-formation, sinusoidal ectasia, small hepatocyte hyperplasia, and increased number of alpha-smooth muscle actin (alpha-SMA)-positive cells. An electron microscopic study disclosed sinusoidal endothelial cell degeneration and injury in the liver of TCDD-treated monkeys. Western blot analysis showed downregulation of aryl hydrocarbon receptor (AhR) protein expression and decreased level of vascular endothelial (VE) cadherin but increased expression levels of CYP1A1 and transforming growth factor beta (TGF-beta) protein in the liver tissues. These changes observed in TCDD-exposed monkeys indicated sinusoidal endothelial cell injury and impairment in intrasinusoidal microcirculation. Infarction, focal fatty change, and microthrombi-formation are considered to be closely associated with intrahepatic circulatory impairment. Increased number of alpha-SMA-positive cells and decreased level of VE cadherin expression in the liver tissues might also be associated with sinusoidal endothelial cell injury. In addition, downregulation of AhR expression and increased CYP1A1 protein levels in the liver were consistent with persistent effects of TCDD. Although it has been reported that TCDD induced endothelial cell injury, this is the first report to describe vascular disorders and protein expression in the liver after injection with TCDD in a primate model.

Objective: Estrogens and estrogen-like substances have been reported to play an important role in male bone homeostasis and to prevent bone loss. Pueraria mirifica (Leguminosae), a Thai herbal plant, containing a high amount of phytoestrogens was a choice of interest for this study. We examined the effects of crude P. mirifica on bone loss and influences on reproductive organs in male rats. Methods: Using fully mature and orchidectomized (ORX) rats, the effects of 0, 10, 100 and 1000 mg/kg B.W./day of P. mirifica and 0.1 mg/kg B.W./day of 17 alpha-ethinylestradiol (a positive control) were evaluated on bone mineral density (BMD) and bone mineral content (BMC) measured with a peripheral Quantitative Computerized Tomography (pQCT) densitometry. Results: Bone loss in trabecular and cortical bones of the various sites of axial bone (fourth lumbar vertebral body) and long bones (tibia and femur) after ORX was dose-dependently prevented by P. mirifica. The effects were specific on bone types and sites. The weights of the accessory sex organs, seminal vesicle and ventral prostrate gland, which significantly decreased after 3-month of ORX, were not altered by P. mirifica. Conclusion: The results suggest that P. mirifica treatment may be useful to prevent an osteoporosis in elderly hypogonadism subjects without influences on reproductive organs. © 2006 Elsevier Ireland Ltd. All rights reserved.

A cDNA encoding a novel cytochrome P450 1A2 (CYP1A2) was cloned from the liver of an adult female Japanese monkey. The CYP1A2 protein was expressed in yeast cells and its enzymatic properties were compared with those of marmoset CYP1A2 using ethoxyresorufin (ER) and phenacetin (PN) as substrates. The nucleotide sequence of Japanese monkey CYP1A2 revealed 94.7, 99.5 and 93.5% identities to those of human, cynomolgus monkey and marmoset monkey CYP1A2, respectively. Multiple amino acid sequence alignment of Japanese monkey CYP1A2 with CYP1A2 of humans, cynomolgus monkeys and marmosets showed that Japanese monkey CYP1A2 had 92.4, 99.0 and 91.9% identities to the human, cynomolgus monkey and marmoset enzymes, respectively. Kinetic studies demonstrated that the enzymatic properties as ER and PN O -deethylases were considerably different between the Japanese monkey and the marmoset CYP1A2. Furthermore, both of these reactions in liver microsomal fractions from the Japanese monkey and marmoset showed biphasic kinetics. On the basis of the kinetic parameters, it is suggested that Japanese monkey CYP1A2 is a high- K m enzyme in both ER and PN O -deethylations, whereas marmoset CYP1A2 is a high- K m and low- K m enzyme in ER and PN O -deethylations, respectively. α-Naphthoflavone, an inhibitor of human CYP1A1 and CYP1A2, did not completely inhibit the liver microsomal oxidations of ER and PN even at the highest concentration (50 μM), supporting the notion that CYP1A2 enzymes are not the sole ER or PN O -deethylase in Japanese monkey and marmoset liver microsomes. Inhibitory effects of furafylline, an inhibitor of human CYP1A2, on ER O -deethylation by recombinant CYP1A2 enzymes were much lower than those of α-naphthoflavone, but marmoset CYP1A2 was more sensitive to furafylline than Japanese monkey CYP1A2. These results indicate that the properties of Japanese monkey CYP1A2 are considerably different from those of marmoset CYP1A2.

A cDNA was cloned from Japanese monkey liver mRNA by reverse transcriptase–polymerase chain reaction (RT–PCR) using oligonucleotide primers based on the marmoset cytochrome P450 2D19 (CYP2D19) nucleotide sequence. The full-length cDNA encoded a 497 amino acid protein (designated CYP2D29) that is 96, 91, and 88% homologous to human CYP2D6, cynomolgus monkey CYP2D17, and marmoset monkey CYP2D19, respectively. Yeast cells ( Saccharomyces cerevisiae AH-22 strain) transfected with pGYR1 vectors containing the CYP2D29 cDNA were cultured, and microsomal fractions were obtained. Reduced carbon monoxide-difference spectra and western blot analysis using polyclonal antibodies raised against rat CYP2D2 demonstrated that in yeast cell microsomal fractions, the level of CYP2D29 holoenzyme was similar to that of CYP2D6 holoenzyme. However, western blot analysis indicated that the level of CYP2D29 in Japanese monkey liver microsomes might be much higher than that of CYP2D6 in human liver microsomes. Japanese monkey liver microsomes exhibited much higher activities than did human liver microsomes, expressed as nmol/min/mg protein, for debrisoquine (DB) 4-hydroxylation and bufuralol (BF) 1″-hydroxylation (typical reactions catalyzed by CYP2D6), whereas recombinant CYP2D29 activity, expressed as nmol/min/nmol CYP, was similar to that of CYP2D6 for DB and BF hydroxylation. In kinetic analyses, the K m value of CYP2D29 for DB 4-hydroxylation was much lower than that of Japanese monkey liver microsomes, whereas the K m value of CYP2D6 for DB 4-hydroxylation was similar to that of human liver microsomes. In contrast, K m values for BF 1″-hydroxylation were similar for Japanese monkey and human liver microsomes and yeast cell microsomal fractions expressing recombinant CYP2D29 or CYP2D6. These results suggest that the properties of Japanese monkey CYP2D29 are similar to those of human CYP2D6, but their populations and/or some other factors in liver microsomes may cause the difference in microsomal DB 4-hydroxylase activities between Japanese monkeys and humans.

Placental transfer of bisphenol-A (BPA) was studied in mice and Japanese monkeys (Macaca fuscata). BPA was found in maternal and fetal sera, liver, brain, uteri, testes and placenta as early as 30 min after a single subcutaneous (s.c.) injection to 17 days of pregnancy in mice. BPA was also found in fetal liver, kidney, and brain of Japanese monkeys 1 hr after a single s.c. injection to 150 days of pregnancy. These results clearly indicate that the maternal placental barrier can not protect the fetus from the consequences of BPA exposure in these species.

TRF (terminal restriction fragments) length in various tissues of non-human primates such as Macaca mulatta (rhesus monkey), Macaca fuscata (Japanese monkey), Macaca fascicularis (crab-eating monkey), Pan troglodytes (common chimpanzee), and Pongo pygmaeus (orangutan) was at least 23 kb without exception, which was quite different from that of human somatic tissues (smaller than 10 kb). The distribution pattern of telomerase activity among tissues was similar between human and non-human primates, while the activity level showed some differences such as that strong telomerase activity was observed in gastrointestinal and lymphocytic tissues from non-human primates. The human appears to be a unique species among primates in terms of telomere length.

The stereoselectivity in 4-hydroxylation of bunitrolol (BTL), a beta-adrenoreceptor blocking agent, was examined in liver microsomes from monkeys (marmosets and Japanese monkeys) and compared with the results of human liver microsomes. The formation of (+)-4-OH-BTL from (+)-BTL from (+)-BTL was significantly higher than that of (-)-4-OH-BTL from (-)-BTL in the liver microsomal fractions from the two kinds of monkeys. The 4-OH-BTL-forming activity from racemic BTL was significantly lower than from enantiomeric BTL, indicating a possible metabolic interaction between BTL enantiomers. The in vitro profiles observed in the monkeys were very similar to those in humans, but the stereoselectivity in BTL metabolism [(+)-BTL > (-)-BTL] in the primates was found to be reverse to that in rats [S. Narimatsu et al., Anal. Biochem., 222, 256-261 (1994)]. The 4-OH-BTL-forming activity from BTL enantiomers was significantly suppressed by quinidine and quinine, while the former was more potent than the latter, and also by alpha-naphthoflavone. Furthermore, the activity was also suppressed by antisera against rat cytochromes P450-2D2 and -1A2 in concentration-dependent manners. However, kinetics showed that enantiomeric BTL 4-hydroxylation was monophasic in liver microsomes from marmosets of both genders and from male Japanese monkeys. These results suggest that cytochrome P450-2D and -1A enzymes with similar Km values are involved in BTL 4-hydroxylation in monkey liver microsomes.

Two species of African Solanum (Solanaceae), S. dasyphyllum and S. aculeastrum, in the tropical montane forest in Zaire were found to be eaten and seed-dispersed only by elephants. No other animal is suggested to eat these fruits owing to the poisonous substances in fruits. It requires more substantial support, but this can be the first case reported that plants chose the special animals as the seed disperser by chemical means.

We thought to validate the current tolerable daily intake (TDI) value for dioxin (4 pg/kg) in Japan. Pregnant rhesus monkeys received an initial dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0, 30, or 300 ng/kg subcutaneously) on day 20 of gestation; the dams received additional injection of 5% of the initial dose every 30 days until day 90 after delivery. The teeth of stillborn, postnatally dead, and surviving offspring (now approximately 4 years old) were evaluated. None of the offspring in the 0 and 30 ng/kg groups (n = 17 and 15, respectively) had tooth abnormalities, whereas 10 of 17 in the 300 ng/kg had them. These findings suggest the lowest-observed adverse-effect level (LOAEL) for TCDD in the rhesus monkey is between 30 and 300 ng/kg, and probably is close to that for rodents (86 ng/kg) on which the current TDI was based. It is reasonable to conclude that the current TDI needs no immediate modification.

Using a primer set designed on the cDNA encoding the known marmoset cytochrome P450 2D19 (CYP2D19), a cDNA encoding a novel CYP2D enzyme (CYP2D30) was cloned from the liver of a female marmoset bred at Kyoto University (KYU). In addition, a cDNA encoding CYP2D19 was cloned from the liver of a female marmoset bred at Kagoshima University (KAU). CYP2D30 and CYP2D19 showed homologies of 93.6 and 93.4% in their nucleotide and amino acid sequences, respectively. Reverse transcription polymerase chain reaction (RT-PCR) and digestion with NdeI demonstrated that the KYU-marmoset liver contained mainly mRNA for CYP2D30, while the KAU-marmoset liver contained mainly mRNA for CYP2D19. Marmoset CYP2D30, like human CYP2D6, exhibited high debrisoquine (DB) 4-hydroxylase activity and relatively low DB 5-, 6-, 7- and 8-hydroxylase activities, whereas CYP2D19 lacked DB 4-hydroxylase but exhibited marked 5-, 6-, 7- and 8-hydroxylase activities. The two marmoset recombinant enzymes showed enantioselective bufuralol (BF) 1″-hydroxylase activities, similar to CYP2D6. BF 1″-hydroxylation by CYP2D30 exhibited product-enantioselectivity of (1″R-OH-BF ⪡ 1″S-OH-BF), similar to that observed with human CYP2D6, whereas CYP2D19 showed a reversed selectivity of (1″R-OH-BF ≥ 1″S-OH-BF). BF 1″-hydroxylation in marmoset liver microsomes from both sources was inhibited by antibodies raised against rat CYP2D1 in a concentration-dependent manner. A known inhibitor of CYP2D6, quinidine, effectively inhibited the BF 1″-hydroxylation activities in liver microsomal fractions prepared from KYU- and KAU-marmosets. These results suggest that CYP2D19 and CYP2D30 proteins can be expressed as functional enzymes in marmoset livers, although it is unresolved whether both enzymes coexist in the same marmoset liver.

We developed a new high-performance liquid chromatographic method using an ODS column and a chiral column for the assay of racemic 4-OH-PL sulfate and enantiomeric 4-OH-PL sulfates, respectively. The method was successfully applied to measure phenolsulfotransferase (PST) activities for 4-OH-PL in cytosolic fractions from livers of Japanese monkeys (Macaca fuscata) and for comparison with its activity of cytosolic fractions from rat, rabbit, dog, and human livers and Hep G2 cells. The activity was ranked as Hep G2 cells > monkeys = humans = dogs = rats > rabbits. To evaluate the Japanese monkey as a nonhuman animal model in drug metabolism studies, we further characterized sulfation of 4-OH-PL as a further metabolic pathway in monkey livers to compare that with human livers. Inhibition studies in which cytosolic fractions were preincubated at 43 degrees C or 2,6-dichloro-4-nitrophenol (DCNP) used as a PST inhibitor indicated that two kinds of PSTs, thermolabile, low-Km and DCNP-resistant PST and thermostable, high-Km and DCNP-sensitive PST were involved in 4-OH-PL sulfation by monkey liver cytosol, which is very similar to the reported profile of 4-OH-PL sulfation by human liver cytosol. Sulfation kinetics in a low concentration range of 4-OH-PL enantiomers demonstrated that apparent Km values were similar between human and monkey liver cytosolic fractions, but the Vmax values were different, so that intrinsic clearance values (Vmax/Km, Clint) were higher in monkeys than in humans. Furthermore, enantiomer selectivity of [R(+)-4-OH-PL > S(-)-4-OH-PL] was observed in the Vmax and CLint values of monkey liver cytosol. These results indicate that the profile of sulfation of 4-OH-PL by liver cytosolic fractions is similar in humans and Japanese monkeys.

We examined and compared enantioselectivity in the oxidation of propranolol (PL) by liver microsomes from humans and Japanese monkeys (Macaca fuscata). PL was oxidized at the naphthalene ring to 4-hydroxypropranolol, 5-hydroxypropranolol and side chain N-desisopropylpropranolol by human liver microsomes with enantioselectivity of [R(+)S(-)] in PL oxidation rates at substrate concentrations of 10 microM and 1 mM. In contrast, reversed enantioselectivity [R(+)S(-)] in PL 5-hydroxylation and N-desalkylation rates at the same substrate concentrations was observed in monkey liver microsomes, although the selectivity was the same for PL 4-hydroxylation between the two species. All oxidation reactions of the PL enantiomers in human liver microsomes showed biphasic kinetics, i.e. the reactions could be expressed as the summation of a low-K(m) phase and a high-K(m) phase. Inhibition studies using antibodies and characterization of CYP2D6 enzymes expressed in insect cells or human lymphoblastoid cells indicated that the enantioselectivity of PL oxidation, especially the ring 4- and 5-hydroxylations reflected the properties of CYP2D6 in human liver microsomes. In monkey liver microsomes, all of the oxidation reactions of S(-)-PL showed biphasic kinetics, whereas ring 4- and 5-hydroxylations were monophasic and side chain N-desisopropylation was biphasic for R(+)-PL. Similarly, from the results of inhibition studies using antibodies and inhibitors of cytochrome P450 (P450), it appears that the reversed selectivity [R(+)S(-)] of PL oxidation rates is catalyzed by CYP2D enzyme(s) in monkey liver at low substrate concentrations. These results indicate that different properties of P450s belonging to the 2D subfamily cause the reversed enantioselectivity between human and monkey liver microsomes.

Two isozymes of calpain, mu-calpain and m-calpain, were purified from rabbit, monkey, human and rat tissues to homogeneity and the apparent molecular masses of the large and small subunits of each calpain species were compared directly. While the molecular masses of the small subunits were the same (28 kDa), those of the large subunits were different depending on the calpain type and animal species: Rabbit mu (79 kDa), rabbit m (75 kDa), monkey mu (79 kDa), monkey m (74 kDa), human mu (78 kDa), human m (73 kDa), rat mu (75 kDa), and rat m (74 kDa). Ca2+-sensitivity of monkey mu-calpain was lower than that of rabbit mu-calpain, but m-calpains from rabbit and monkey shared a similar Ca2+-dependency. Immunoreactivities of rabbit, monkey and rat m-calpains towards anti-rabbit m-calpain monoclonal antibodies were different depending on the antibody species, showing the existence of common and different antigenic sites in these three m-calpains. While monkey mu-calpain still showed weak cross-reactivity with anti-rabbit mu-calpain monoclonal antibodies, rat mu-calpain failed to react with any antibody examined, except for the monoclonal 1D10A7 which reacted with mu- and m-calpains from any animal species. Peptides generated by V8 protease digestion were similar between mu-calpains or m-calpains from rabbit and monkey but, again, the reactivity of monkey calpain peptidesto anti-rabbit calpain antibodies was weak, especially to those of mu-calpain.

The primary structure of the parvalbumin (pI4.97) from bullfrog, Rana catesbeiana, skeletal muscle has been determined. It is composed of 110 amino acid residues and a free amino terminus, and has a molecular mass of 11919. The amino add sequences which are thought to be functionally important sites are also conserved in the bullfrog parvalbumin. The calculated phylogenic tree indicates that this parvalbumin belongs to the α group of parvalbumins. The mutation rate of parvalbumin was fairly rapid in frogs compared to mammals. The subdivergence of frogs is also discussed.

1. A high affinity Ca2+ binding and low mol. wt protein, parvalbumin, was purified from monkey skeletal muscle. 2. As compared with other animals, only one component and a lower content of monkey parvalbumin were found. 3. This may suggest that both the component and the content of parvalbumin decreases with biological evolution. 4. The parvalbumin was found to have a mol. wt of 11,400, a pI of 5.1, a high aspartic acid and lysine content, maximum absorption at around 260 nm, a blocked amino-terminal, an immunological distinction, 2 mol Ca2+ binding/mol, and a conformational change by Ca2+ binding. 5. Parvalbumin was shown to have alpha type properties.

The distribution in Japanese monkey tissues of glutathione S-transferase activity toward some aromatic nitro compounds was examined by measuring the release of the nitro group as nitrite ion. The activity was especially high in liver, kidney and small intestine when compounds such as 4-nitroquinoline N-oxide, 5-nitrofurfural diacetal and o-dinitrobenzene were used as substrates. The nitrite-releasing activity of the major enzyme purified from rhesus monkey liver was also tested on fifty-two nitro compounds including nineteen nitrofuran derivatives. Among the thirty-three nitro compounds other than the nitrofuran derivatives tested as substrates, the purified enzyme showed activity only toward o-dinitrobenzene, 4-nitroquinoline N-oxide, 3,4-dinitrobenzoic acid, p-dinitrobenzene, 2,5-dinitrobenzoic acid, 2,5-dinitrophenol, tetra-chloronitrobenzene and 2,4-dinitrobenzoic acid. The crude supernatant fraction of rhesus monkey liver showed activity in substrate specificity roughly similar to that of the purified enzyme. On the other hand, among at least ten carcinogenic 2-substituted 5-nitrofran derivatives tested, 4,6-diamino-2-(5-nitro-2-furyl)-s-triazine, 5-nitro-2-furaldehyde semicarbazone, N-[[3-(5-nitro-2-furyl)-1,2,4-oxadiazol-5-yl]methyl] acetamide, and N-[5-(5-nitro-2-furyl)-1-3,4-thiadiazol-2-yl)acetamide were shown to be enzymatically conjugated with reduced glutathione. Among the other nine 2-substituted 5-nitrofuran derivatives tested, six compounds could be the substrates of the enzyme, and 5-nitrofurfural and 5-nitrofurfural diacetal were especially good substrates. There was, however, little apparent correlation between their carcinogenicity and susceptibility to glutathione S-transferase. The bulky substituents at position 2 appeared to decrease the susceptibility of these nitrofuran derivatives to the enzyme. Both Vmax and Km values of the purified enzyme varied greatly among the substrates, and the optimum pH fell between 7.5 and 9.0 in most cases.

Glutathione S-transferase was purified from porcine brain. Four enzyme fractions were obtained by column chromatography on CM-cellulose and the main enzyme fraction was purified to apparent homogeneity as judged by disc gel electrophoresis. The action spectra of these enzyme fractions toward some typical substrates were roughly similar. The optimum pH range of the purified enzyme was from 6.5 to 7.5 with o-dinitrobenzene as a substrate. The main enzyme showed a molecular weight of about 43,000 on Sephadex G-150 chromatography, and about 22,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was composed of two subunits of apparently identical molecular weight bound to each other noncovalently. The amino acid composition showed characteristic high contents of leucine and glutamic acid residues. A notable difference was observed in the lysine content as compared with that of the liver enzyme. The brain enzyme bound bilirubin less strongly than the monkey liver enzyme and human albumin. In addition, the regional and subcellular distributions of the enzyme in porcine brain was investigated with o-dinitrobenzene as a substrate. The enzyme activity was found to be distributed fairly evenly in various regions of the brain, and was especially abundant in the cytosol fraction. However, the enzyme activity was also detected considerably in the microsomal and mitochondrial fractions but not in the synaptosomal fraction.

Conditions have been investigated for the use of triazine dye agarose as an affinity matrix for the purification of glutathione S-transferases from bovine liver. Orange A agarose was most suitable for this purpose among various dye agaroses tested. The enzymes were adsorbed on the dye agarose column and then completely eluted with the buffer containing 1 mM reduced glutathione. Thus, a simple and rapid method for purification of bovine liver transferases was developed, which uses column chromatographies on orange A agarose followed by DEAE-Sephacel. One step of the affinity chromatography provided 40-fold purification. Upon chromatography on DEAE-Sephacel, the enzyme activity separated into two major forms (I and II), which were purified to apparent homogeneity as examined by polyacrylamide gel electrophoreses. The pI values of the two forms, I and II, were 6.7 and 6.1, respectively. The overall extents of purification of I and II were about 40-fold and 50-fold, respectively. The activities of the two major enzymes toward various substrates were roughly similar. The optimum pH values of these enzymes were 7.5 as measured with o-dinitrobenzene as a substrate. The activities were significantly inhibited by Cu2+, Hg2+, Cd2+, and Zn2+. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both enzymes showed one band with a molecular weight of about 27,000. Both enzymes, however, were eluted as a single peak from a Sephadex G-150 column at a position corresponding to a molecular weight of about 49,000. These results show that each enzyme consists of two subunits bound to each other non-covalently. The amino acid compositions showed characteristically high contents of leucine and aspartic acid residues. Double immunodiffusion showed complete identity of the two forms reacting with both rabbit anti-enzyme sera. The two enzymes had an identical amino-terminal amino acid sequence as follows: H-Pro-Met-Ile-Leu-Gly-Tyr-Trp-Asp-Ile-Arg-Gly-Leu-Ala-His-Ala-Ile-Ser-Le u-Leu-Leu.

The sensitivity of polymorphonuclear leukocytes (PMN) to N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) for chemotaxis and for lysosomal enzyme release was examined using the PMN of four primate species, human (H. sapiens), chimpanzee (P. troglodytes), rhesus monkey (M. mulatta), and cotton-headed tamarin (S. (O) oedipus). The 50 per cent effective concentrations (EC50) of fMet-Leu-Phe for chemotaxis were 2.5 X 10(-9) M in human, 10(-9) M in chimpanzee, 8 X 10(-8) M in rhesus monkey, and 3.3 X 10(-6) M in tamarin. The EC50 values of fMet-Leu-Phe for myeloperoxidase (MPO) release were 10(-8) M in human, 4 X 10(-8) M in chimpanzee, 4 X 10(-8) M in rhesus monkey, and 10(-6) M in tamarin and those for beta-glucuronidase release were 4 X 10(-9) M, 6.4 X 10(-8) M, 1.8 X 10(-7) M, and 1.6 X 10(-6) M, respectively. Thus, the sensitivity to fMet-Leu-Phe for chemotaxis was in the order: chimpanzee congruent to human greater than rhesus monkey greater than tamarin, and that for the release of lysosomal enzymes, MPO and beta-glucuronidase, was in the order: human greater than chimpanzee greater than rhesus monkey greater than tamarin. These results appear to indicate that the sensitivity to fMet-Leu-Phe increases in the order of evolution of primates toward the human, and suggest that the sensitivity of PMN in the defence function against infection also increases in the same order.