Tài liệu Báo cáo khoa học: An immunomodulator used to protect young in the pouch of the Tammar

Eugenin

An immunomodulator used to protect young in the pouch of the

Tammar wallaby, Macropus eugenii

Russell V. Baudinette1,*, Pinmanee Boontheung2

, Ian F. Musgrave3

, Paul A. Wabnitz2

,

Vita M. Maselli2

, Jayne Skinner1

, Paul F. Alewood4

, Craig S. Brinkworth2 and John H. Bowie2

1 Department of Environmental Biology, The University of Adelaide, South Australia

2 Department of Chemistry, The University of Adelaide, South Australia

3 Department of Clinical and Experimental Pharmacology, The University of Adelaide, South Australia

4 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia

Marsupials are born in an immature state and many

of the developmental processes that occur in these

mammals take place during pouch life [1]. After a

short period of intrauterine development, the young

marsupial crawls unaided to the mother’s pouch, atta￾ches to a teat, and undergoes further development in

an aerial environment [2] (Fig. 1). The pouch microcli￾mate is characterized by high humidity, and a constant

temperature close to maternal body temperatures [3].

The pouch, with its warm, moist environment, is a

favourable environment for microorganisms. It has

been shown that a variety of Gram-positive bacilli are

present in marsupial pouches, together with lesser

amounts of Gram-negative bacilli [4,5]. The bacterial

content of the pouch diminishes significantly upon

arrival and occupancy of the young marsupial [6].

When the young first crawls into the pouch, it has

essentially no immune system of its own and must

rely on that provided by the mother [1,7], even

though it has been reported that an immunoglobulin

is present in fetal and newborn sera of the Tammar

wallaby (Macropus eugenii) [7]. With increasing devel￾opment, the young produces its own immune system.

For example, T and B cells are first detected 50 days

into the development of the young wallaby in the

pouch [7], and it has been shown that cholecystokinin

8 (CCK8) (a neuropeptide which engenders T and B

cell proliferation) is present in the brains of mature

Keywords

eugenin; immunomodulator; lactating

female; Tammar wallaby (Macropus eugenii)

Correspondence

J. H. Bowie, Department of Chemistry, The

University of Adelaide, South Australia, 5005

Fax: +61 08 83034358

Tel: +61 08 83035767

E-mail: [email protected]

*Author deceased

(Received 30 August 2004, revised 18

October 2004, accepted 16 November

2004)

doi:10.1111/j.1742-4658.2004.04483.x

Eugenin [pGluGlnAspTyr(SO3)ValPheMetHisProPhe-NH2] has been

isolated from the pouches of female Tammar wallabies (Macropus eugenii)

carrying young in the early lactation period. The sequence of eugenin

has been determined using a combination of positive and negative ion

electrospray mass spectrometry. This compound bears some structural

resemblance to the mammalian neuropeptide cholecystokinin 8

[AspTyr(SO3)MetGlyTrpMetAspPhe-NH2] and to the amphibian caerulein

peptides [caerulein: pGluGlnAspTyr(SO3)ThrGlyTrpMetAspPhe-NH2].

Eugenin has been synthesized by a route which causes only minor hydrolysis

of the sulfate group when the peptide is removed from the resin support. Bio￾logical activity tests with eugenin indicate that it contracts smooth muscle at a

concentration of 10)9 m, and enhances the proliferation of splenocytes at

10)7 m, probably via activation of CCK2 receptors. The activity of eugenin

on splenocytes suggests that it is an immunomodulator peptide which plays a

role in the protection of pouch young.

Abbreviations

CCK-8, cholecystokinin 8; CCK-8-NS, cholecystokinin 8 nonsulfated; QTOF, quadrupole-time-of-flight; splenocyte, spleen derived lymphocyte;

TFA, trifluoroacetic acid.

FEBS Journal 272 (2005) 433–443 ª 2005 FEBS 433