Investigation of the mechanisms of anti-complement activity in Ixodes ricinus ticks.
The feeding success of a tick upon a host depends on its ability to suppress host anti-tick responses which include activation of the complement system. We investigated the mechanism of inhibition of the alternative pathway of complement by salivary gland extract (SGE) of the ixodid tick species, Ixodes ricinus. SGE treatment strongly inhibited C3a generation and factor B cleavage in serum when rabbit erythrocytes were used as complement activator, but not when cobra venom factor (CVF) was used as an activator. SGE treatment strongly inhibited C3b deposition on rabbit erythrocytes, and the turnover of C3 (to C3b/iC3b) in serum. However, there was no significant effect upon the formation, stability or activity of C3 convertase (C3bBb) when formed from purified C3b, factor B and factor D. SGE treatment of isolated C3 resulted in a shift in mobility of the alpha-chain (by about 5 kDa). N-terminal sequencing of this species suggests that cleavage occurs at the C-terminus of the alpha-chain of C3. Consistent with this hypothesis, the modified alpha-chain was still a substrate for pre-formed convertase. The activity was specific for the alpha-chain of C3 but not of C3(H2O) nor the alpha'-chain of C3b. It is proposed that SGE-modified C3 does not participate in convertase formation, probably having a reduced affinity for factor B.
LRF Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Level 5, Academic Block, University of Oxford, Oxford OX3 9DU, UK. charles.lawrie@ndcls.ox.ac.uk
Charles H
CH
Lawrie
Robert B
RB
Sim
Patricia A
PA
Nuttall
D000818:Animals; D002457:Cell Extracts / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D051561:Complement C3 Convertase, Alternative Pathway; D015926:Complement C3a / Q000037:antagonists & inhibitors / Q000378:metabolism; D003179:Complement C3b / Q000187:drug effects / Q000378:metabolism; D011415:Complement Factor B / Q000037:antagonists & inhibitors / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D006801:Humans; D018884:Ixodes / Q000276:immunology* / Q000472:pathogenicity; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012469:Salivary Glands / Q000737:chemistry*
D002457:Cell Extracts; D010446:Peptide Fragments; D015926:Complement C3a; D003179:Complement C3b; D051561:Complement C3 Convertase, Alternative Pathway; D011415:Complement Factor B