Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes.
Chemotactic factors stimulate a rapid increase in the cytosolic concentration of intracellular calcium ions ([Ca2+]in) in human polymorphonuclear leukocytes (PMNL), which may be an event that is critical to the expression of chemotaxis and other PMNL functions. Treatment of PMNL with pertussis toxin catalyzes ADP-ribosylation of a protein similar or identical to the inhibiting regulatory protein of adenylate cyclase, Gi, and suppresses the increase in [Ca2+]in elicited by leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine. Chemotactic migration and lysosomal enzyme release elicited by chemotactic factors were inhibited by pertussis toxin with a concentration-dependence similar to that for inhibition of the increase in [Ca2+]in, without an effect on lysosomal enzyme release induced by the ionophore A23187 and phorbol myristate acetate. Activated pertussis toxin catalyzed the [32P]ADP-ribosylation of a 41 kD protein in homogenates of PMNL. The extent of [32P]ADP-ribosylation of this protein was reduced 59% by pretreatment of intact PMNL with pertussis toxin. Pertussis toxin selectively decreased the number of high-affinity receptors for LTB4 on PMNL by 60% without altering the number or binding properties of the low-affinity subset of receptors. Pertussis toxin modification of a membrane protein of PMNL analogous to Gi thus simultaneously alters chemotactic receptors and attenuates the changes in cytosolic calcium concentration and PMNL function caused by chemotactic factors.
Goldman
D W
DW
Chang
F H
FH
Gifford
L A
LA
Goetzl
E J
EJ
Bourne
H R
HR
D000246:Adenosine Diphosphate Ribose / Q000097:blood; D037361:Adenylate Cyclase Toxin; D001427:Bacterial Toxins / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000097:blood; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin; D011971:Receptors, Immunologic / Q000187:drug effects; D018102:Receptors, Leukotriene B4; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D001427:Bacterial Toxins; D002630:Chemotactic Factors; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D005966:Glucuronidase; D019204:GTP-Binding Proteins; D002118:Calcium