| 摘要 |
Disclosed is a 6 kDa host-defense polypeptide which is generated by proteolitic digestion of the lactoferrin molecule. The 6 kDa host-defense polypeptide has antimicrobial activity and also endotoxin-neutralizing activity. Also disclosed are functional variants of the 6 kDa host defense polypeptide, which include N-terminal and C-terminal truncations of the 6 kDa polypeptide, and other modifications of the polypeptide, such as amino acid substitutions which preserve or enhance activity. Another aspect of the present invention relates to a therapeutic method for treating or preventing a disease resulting from microbial bacterial or fungal infections in an individual. Another aspect of the present invention is the use of the 6 kDa LF polypeptide and functional variants thereof to potentiate the therapeutic action of an antimicrobial drug in a patient. In another aspect, the present invention relates to a method for neutralizing circulating endotoxin in a patient by administering the endotoxin-neutralizing polypeptide or functional variant thereof of the present invention to the patient. Also encompassed within the scope of the invention are methods for potentiating the endotoxin-neutralizing and antimicrobial activity of the polypeptide of the present invention. In addition, methods for increasing the in vivo production of the 6 kDa LF fragment in a patient by in vivo proteases are also disclosed. |
