Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

TY - JOUR

T1 - Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

AU - Sørensen, A L

AU - Hey, A S

AU - Kharazmi, A

N1 - Keywords: Animals; Chemiluminescent Measurements; Chemotaxis, Leukocyte; Humans; Leishmania major; Membrane Glycoproteins; Metalloendopeptidases; Monocytes; Neutrophils; Protozoan Proteins; Respiratory Burst

PY - 1994

Y1 - 1994

N2 - In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63 in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished by heat inactivation of the protease at 70 degrees C for 15 min. Neither neutrophil nor monocyte chemiluminescence was inhibited by Gp63 when cells were stimulated with PMA. Our data suggest that the major surface protease Gp63 might play an important role in the initial stages of Leishmania/macrophage interactions and the intracellular survival of the parasite.

AB - In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63 in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished by heat inactivation of the protease at 70 degrees C for 15 min. Neither neutrophil nor monocyte chemiluminescence was inhibited by Gp63 when cells were stimulated with PMA. Our data suggest that the major surface protease Gp63 might play an important role in the initial stages of Leishmania/macrophage interactions and the intracellular survival of the parasite.

M3 - Journal article

C2 - 8011303

SN - 0903-465X

VL - 102

SP - 265

EP - 271

JO - APMIS. Supplementum

JF - APMIS. Supplementum

IS - 4

ER -