Differential mechanisms in the stimulus-secretion coupling in human basophils: evidence for a protein-kinase-C-dependent and a protein-kinase-C-independent route.
Upon activation, basophilic granulocytes release inflammatory mediators, such as histamine. We studied histamine release (HR) of purified (64 +/- 10%) human basophils after cross-linking of membrane-bound IgE via anti-IgE or after binding of the chemoattractant formyl-methionyl-leucyl-phenylalanine (FMLP). A variability in the extent of histamine release upon stimulation by either anti-IgE or FMLP was found between donors. Non-responders for FMLP showed high histamine release for anti-IgE, and vice versa. Inhibition of protein kinase C (PKC) by staurosporine (STSP) resulted in partial inhibition of the anti-IgE-induced HR, whereas inhibition of a PKC-independent pathway by wortmannin (WTM) totally blocked the anti-IgE induced histamine release. The HR induced by FMLP was not affected by either of these inhibitors. We conclude that major differences exist in the signal-response coupling between the anti-IgE and FMLP-induced HR in human basophils. The so-called releasability of human basophils may be due to the availability of different cell activation pathways.
Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
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EF
Knol
L
L
Koenderman
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E
Mul
A J
AJ
Verhoeven
D
D
Roos
D000470:Alkaloids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001491:Basophils / Q000201:enzymology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D019311:Staurosporine; D000077191:Wortmannin