Interaction of Ceruloplasmin, Lactoferrin, and Myeloperoxidase

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A. V. Sokolov^1*, M. O. Pulina¹, K. V. Ageeva¹, M. I. Ayrapetov¹, M. N. Berlov¹, G. N. Volgin², A. G. Markov², P. K. Yablonsky², N. I. Kolodkin³, E. T. Zakharova¹, and V. B. Vasilyev¹

¹Institute for Experimental Medicine, Russian Academy of Medical Sciences, ul. Akademika Pavlova 12, 197376 St. Petersburg, Russia; fax: (812) 234-9489; E-mail: biochem@nm.ru

²Medical Faculty, St. Petersburg State University, 21-ya Liniya V.O. 8A, 199106 St. Petersburg, Russia; fax: (812) 774-9367

³State Research Institute for Highly Pure Biopreparations, ul. Pudozhskaya 7, 197110 St. Petersburg, Russia; fax: (812) 235-5504

^* To whom correspondence should be addressed.

Received November 24, 2006; Revision received December 21, 2006

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When lactoferrin (LF) and myeloperoxidase (MPO) are added to ceruloplasmin (CP), a CP-LF-MPO triple complex forms. The complex is formed under physiological conditions, but also in the course of SDS-free PAGE. Polyclonal antibodies to both LF and MPO displace the respective proteins from the CP-LF-MPO complex. Similar replacement is performed by a PACAP38 fragment (amino acids 29-38) and protamine that bind to CP. Interaction of LF and MPO with CP-Sepharose is blocked at ionic strength above 0.3 M NaCl and at pH below 4.1 (LF) and 3.9 (MPO). Two peptides (amino acids 50-109 and 929-1012) were isolated by affinity chromatography from a preparation of CP after its spontaneous proteolytic cleavage. These peptides are able to displace CP from its complexes with LF and MPO. Both human and canine MPO could form a complex when mixed with CP from seven mammalian species. Upon intravenous injection of human MPO into rats, the rat CP-human MPO complex could be detected in plasma. Patients with inflammation were examined and CP-LF, CP-MPO, and CP-LF-MPO complexes were revealed in 80 samples of blood serum and in nine exudates from purulent foci. These complexes were also found in 45 samples of serum and pleural fluid obtained from patients with pleurisies of various etiology.

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KEY WORDS: ceruloplasmin, lactoferrin, myeloperoxidase, protein-protein interactions

DOI: 10.1134/S0006297907040074

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