Relationship between the transient cAMP increase, exocytosis from specific and azurophil granules and chemotaxis in neutrophil granulocytes.
The short transient increase of the intracellular cAMP concentration during the first minute following stimulation, exocytosis from specific and azurophil granules, random and directional locomotion were assessed following stimulation of human and equine neutrophils with f-Met-Leu-Phe, C5ades Arg, standard gamma globulin (SGG) and the ionophore A23187. Different leucocyte-activating agents elicited distinct patterns of responses. The results showed that: Chemotactic factors produced exocytosis of small amounts of vitamin B12-binding proteins but not beta-glucuronidase, in the absence of cytochalasin B. Chemotaxis, the appearance of the transient cAMP peak and exocytosis from specific granules in response to cytotaxins were strictly correlated in the absence of cytochalasin B but not if exocytosis was measured in the presence of cytochalasin B. Thus comparison of exocytosis measured in the presence of cytochalasin B with other functions may be misleading. The non-chemotactic agents tested (SGG, A23187) produced secretion but no cAMP peak within 1 minute after stimulation, indicating that the cAMP peak is no obligatory event for triggering exocytosis in general. The ionophore A23187 alone at a concentration of 10(-6) M produced exocytosis from specific granules only, increased motility of cells in suspension and a marked increment of neutrophil adhesion to glass and after a lag period a sustained increase in cAMP. SGG elicited release of both vitamin B12-binding proteins and beta-glucuronidase.
D000001:Calcimycin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003182:Complement C5 / Q000031:analogs & derivatives / Q000494:pharmacology; D015937:Complement C5a, des-Arginine; D000242:Cyclic AMP / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D005719:gamma-Globulins / Q000494:pharmacology
D003182:Complement C5; D015937:Complement C5a, des-Arginine; D005719:gamma-Globulins; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP