Binding of tissue-type plasminogen activator (t-PA) to Neisseria meningitidis and Haemophilus influenzae.
Forty-nine bacterial strains representing five species known to interact with human plasminogen were tested for the ability to bind the two major human plasminogen activators, t-PA and urokinase. The bacterial species tested included Haemophilus influenzae, Neisseria meningitidis, Streptococcus pyogenes, Streptococcus equisimilis and human group G streptococci. All N. meningitidis and 11 of 14 H. influenzae strains displayed substantial binding of t-PA with values in the range of 20-46%. On the contrary, none of the streptococcal strains bound significant amounts of tPA. With urokinase no binding could be found for any of the bacterial species tested. Scatchard analysis with a selected H. influenzae strain (HI23354) demonstrated 10,000 receptors per bacterium for t-PA with a Kd value of about 20 nmol l-1. The corresponding values with a selected N. meningitidis strain (Mo 52) was 8500 receptors per bacterium and 70 nmol l-1. t-PA binding could be reduced about 40% by the addition of 10 mmol l-1 of the lysine analogue epsilon-aminocaproic acd (EACA) whereas no inhibitory effect could be demonstrated with arginine. Addition of 2 mumol l-1 of plasminogen which is enough to occupy all bacterial sites for plasminogen did not interfere with the t-PA binding, suggesting that the receptors for t-PA and plasminogen are distinct. Using very high plasminogen concentrations however, t-PA binding could be reduced by about 50% possibly due to an interaction between t-PA and plasminogen in the fluid phase. Our results demonstrate the occurrence of a previously unknown type of bacterial receptor that is capable of specifically binding t-PA.
Ullberg
M
M
Department of Clinical Microbiology, Karolinska Hospital, Stockholm, Sweden.
Wiman
B
B
Kronvall
G
G
D015119:Aminocaproic Acid / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000378:metabolism*; D010958:Plasminogen / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D010958:Plasminogen; D001120:Arginine; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D015119:Aminocaproic Acid