Bacterial chaperone protein, Skp, induces leukocyte chemotaxis via C5a receptor.
C5a receptor has been identified as a leukocyte chemotactic receptor to two intrinsic chemical mediators, C5a and the S19 ribosomal protein dimer, so far. We found an Escherichia coli protein that also induced the chemotactic responses of monocytes and polymorphonuclear leukocytes via the C5a receptor. We identified the E. coli-derived chemoattractant to be Skp by the molecular size and the N-terminal amino acid sequence. Skp is a periplasmic chaperone protein widely present in gram-negative bacterial species. Immunoabsorption experiments indicated that Skp was the major leukocyte chemotactic factor in the E. coli extract. Receptor-antagonizing experiments with analogue peptides of S19 ribosomal protein and of C5a suggested that Skp induced the receptor activation by the two-step binding mechanism as in the cases of the intrinsic mediators, sharing the ligand-binding site of the receptor among them at each binding step. The C5a receptor would play a role in the host defense directly recognizing the bacteria-derived protein, besides identifying the signals of the intrinsic chemical mediators.
Department of Molecular Pathology, Faculty of Medical and Pharmaceutical Sciences, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan.
Arjun
A
Shrestha
Lei
L
Shi
Sumio
S
Tanase
Makiko
M
Tsukamoto
Norikazu
N
Nishino
Kazutaka
K
Tokita
Tetsuro
T
Yamamoto
D000818:Animals; D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D044087:Receptor, Anaphylatoxin C5a; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; C072721:Skp protein, E coli; D015936:Complement C5a